Targeted antimicrobial moieties

ABSTRACT

This invention provides novel targeted antimicrobial compositions. In various embodiments chimeric moieties are provided comprising an antimicrobial peptide attached to a peptide targeting moiety that binds a bacterial strain or species.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a Divisional of U.S. Ser. No. 12/683,160, filed Jan. 6, 2010, which claims benefit of and priority to U.S. Ser. No. 61/142,830, filed Jan. 6, 2009, U.S. Ser. No. 61/151,445, filed Feb. 10, 2009, U.S. Ser. No. 61/243,905, filed Sep. 18, 2009, and U.S. Ser. No. 61/243,930, filed Sep. 18, 2009, all of which are incorporated herein by reference in their entirety for all purposes.

STATEMENT OF GOVERNMENTAL SUPPORT

[Not Applicable]

FIELD OF THE INVENTION

The present invention relates to novel targeting peptides, novel antimicrobial peptides, chimeric moieties comprising novel targeting and/or novel antimicrobial peptides and uses thereof.

BACKGROUND OF THE INVENTION

Antibiotic research at the industrial level was originally focused on the identification of refined variants of already existing drugs. This resulted example, in the development of antibiotics such as newer penicillins, cephalosporins, macrolides, and fluoroquinolones.

However, resistance to old and newer antibiotics among bacterial pathogens is evolving rapidly, as exemplified by extended beta-lactamase (ESBL) and quinolone resistant gram-negatives, multi-resistant gonococci, methicillin resistant Staphylococcus aureus (MRSA), vancomycin resistant enterococci (VRE), penicillin non-susceptible pneumococci (PNSP) and macrolide resistant pneumococci and streptococci (see, e.g., Panlilo et al. (1992) Infect Control Hosp Epidemio., 13: 582-586; Morris et al. (1995) Ann Intern Me., d 123: 250-259, and the like). An overuse, or improper use, of antibiotics is believed to be of great importance for triggering and spread of drug resistant bacteria. Microbes have, in many cases, adapted and are resistant to antibiotics due to constant exposure and improper use of the drugs.

Drug resistant pathogens represent a major economic burden for health-care systems. For example, postoperative and other nosocomial infections will prolong the need for hospital care and increase antibiotic drug expenses. It is estimated that the annual cost of treating drug resistant infections in the United States is approximately $5 billion.

SUMMARY OF THE INVENTION

In certain embodiments, novel targeting moieties (e.g., peptides) that specifically/preferentially bind to microorganisms (e.g., certain bacteria, yeasts, fungi, molds, viruses, algae, protozoa, and the like) are provided. The targeting moieties can be attached to effectors (e.g., detectable labels, drugs, antimicrobial peptides, etc.) to form chimeric constructs for specifically/preferentially delivering the effector to and/or into the target organism. In certain embodiments novel antimicrobial peptides that can be used to inhibit (e.g., kill and/or inhibit growth and/or proliferation) of certain microorganisms (e.g., certain bacteria, yeasts, fungi, molds, viruses, algae, protozoa, and the like) are provided.

Accordingly, in certain embodiments, a chimeric construct (chimeric moiety) is provided comprising: an effector attached to a peptide targeting moiety comprising an amino acid sequence found in Table 3 and/or Table 12; and/or an antimicrobial peptide comprising an amino acid sequence found in Table 4 and/or Table 5 attached to a targeting moiety. In certain embodiments the targeting moiety is a peptide comprising an amino acid sequence of a peptide found one or more of Table 3 and Table 12. In certain embodiments the targeting moiety is a peptide comprising two or more amino acid sequences of a peptide found one or more of Table 3 and Table 12. In certain embodiments the targeting moiety is a peptide whose amino acid sequence consists of the amino acid sequence of a peptide found in Table 3.

In various embodiments the effector comprises a moiety selected from the group consisting of an antimicrobial peptide, an antibiotic, a ligand, a lipid or liposome, a agent that physically disrupts the extracellular matrix within a community of microorganisms, and a polymeric particle. In certain embodiments the effector comprises an antimicrobial peptide comprising an amino acid sequence found in one or more of Tables 4, 5, 14, and Table 15. In certain embodiments the effector comprises an antimicrobial peptide comprising an amino acid sequence found in one or more of Tables 4, and 5. In certain embodiments the effector comprises an antimicrobial peptide comprising an amino acid sequence characterized by a motif selected from the group consisting of KIF, FIK, KIH, HIK, and KIV (e.g., as identified in Table 7). In certain embodiments the construct comprises a targeting peptide comprising an amino acid sequence found in Table 3 attached to an antimicrobial peptide comprising an amino acid sequence found in Table 4 and/or Table 5. In certain embodiments the construct comprises an antimicrobial peptide comprising an amino acid sequence found in Table 4 attached to a targeting moiety comprising an amino acid sequence found in Table 3 and/or Table 10, and/or Table 12. In certain embodiments the construct comprises a targeting peptide comprising an amino acid sequence found in Table 3 attached to an antimicrobial peptide comprising an amino acid sequence found in Table 4.

In various embodiments the targeting moiety is chemically conjugated to the effector (directly or via a linker). In certain embodiments the linker comprises a polyethylene glycol (PEG). In certain embodiments the targeting moiety is chemically conjugated to the effector via a non-peptide linker found in Table 16. In certain embodiments the targeting moiety is linked to the effector via a peptide linkage. In certain embodiments the effector comprises an antimicrobial peptide and the construct is a fusion protein. In certain embodiments the targeting moiety is attached to the effector by a peptide linker comprising or consisting of an amino acid sequence found in Table 16. In certain embodiments any of the constructs and/or peptides described herein bears one or more protecting groups. In certain embodiments the one or more protecting groups are independently selected from the group consisting of acetyl, amide, 3 to 20 carbon alkyl groups, fmoc, tboc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, xanthyl (Xan), trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), benzyloxy (BzlO), benzyl (Bzl), benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), benzyloxymethyl (Bom), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), and trifluoroacetyl (TFA). In certain embodiments the peptide and/or construct comprises a protecting group at a carboxyl and/or amino terminus. In certain embodiments the carboxyl terminus is amidated and/or the amino terminus is acetylated. In various embodiments the chimeric construct and/or peptide is functionalized with a polymer (e.g., comprises polyethylene glycol, cellulose, modified cellulose, dextrin, etc.) to increase serum halflife.

In certain embodiments pharmaceutical compositions are provided. In various embodiments the pharmaceutical compositions comprise a chimeric construct as described herein (e.g., a chimeric construct as recited in the claims) and/or an antimicrobial peptide as described herein, in a pharmaceutically acceptable carrier. In certain embodiments the composition is formulated as a unit dosage formulation. In certain embodiments the composition is formulated for administration by a modality selected from the group consisting of intraperitoneal administration, topical administration, oral administration, inhalation administration, transdermal administration, subdermal depot administration, systemic IV application, ocular administration, and rectal administration.

In certain embodiments isolated antimicrobial peptides are provided. In various embodiments the peptides comprise one or more sequences selected from the amino acid sequences listed in Table 4 and/or Table 5 (and/or the retro, inverso, retroinverso, or beta forms). In various embodiments the antimicrobial peptide bears one or more protecting groups e.g., as described herein.

In certain embodiments a composition effective to kill or to inhibit the growth and/or of a microorganism and/or the formation and/or maintenance of a biofilm is provided. The composition typically comprises one or more isolated antimicrobial peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the amino acid sequences listed in Table 4 and/or Table 5 (and/or their retro, inverso, or retroinverso forms). In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of a yeast or fungus, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified (e.g., in those tables) as effective to effective to kill or inhibit the growth and/or proliferation of a yeast or fungus. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of Aspergillus niger and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of Aspergillus niger. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of C. albicans and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of C. albicans. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of T. rubrum and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of T. rubrum. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of a bacterium, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of a bacterium. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of a gram positive bacterium, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of a gram positive bacterium. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of A. naeslundii, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of A. naeslundii. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of B. subtilis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of B. subtilis. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of C. difficile, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of C. difficile. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of C. jeikeium, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of C. jeikeium. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of E. faecalis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of E. faecalis. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of M. luteus, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of M. luteus. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of MRSA, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of MRSA. In certain embodiments composition is effective to kill or inhibit the growth and/or proliferation of S. epidermidis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of S. epidermidis. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of S. mutans, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of S. mutans. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of S. pneumoniae, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of S. pneumoniae. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of a gram negative bacterium, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of a gram negative bacterium. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of A. baumannii, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of A. baumannii. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of C. jejuni, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of C. jejuni. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of E. coli, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of E. coli. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of F. nucleatum, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of F. nucleatum. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of E. coli, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of M. xanthus. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of P. aeruginosa, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of P. aeruginosa. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of P. gingivalis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of P. gingivalis. In certain embodiments the composition is effective to kill or inhibit the growth and/or proliferation of P. mirabilis, and the composition comprises one or more peptides, the amino acid sequences of the peptides comprising one or more sequences selected from the group of amino acid sequences listed in Table 4 and/or Table 5 identified as effective to effective to kill or inhibit the growth and/or proliferation of P. mirabilis.

In various embodiments one or more of the peptides comprising the composition comprise all “L” amino acids or all “D” amino acids, or a mixture of “L” and “D” amino acids. In various embodiments one or more of the peptides comprising the composition are β peptides. In various embodiments one or more of the peptides comprising the composition comprise one or more protecting groups (e.g. protected carboxyl and/or amino termini). In various embodiments one or more of the peptides comprising the composition comprise an amide on the carboxyl terminus and/or an acetyl on the amino terminus. In various embodiments the peptides comprising the composition are in a pharmaceutically acceptable carrier. In certain embodiments the carrier is suitable for administration via a route selected from the group consisting of topical administration, aerosol administration, administration via inhalation, oral administration, and/or rectal administration.

In various embodiments methods are provided for killing and/or inhibiting the growth and/or proliferation of a microorganism and or for disrupting and/or inhibiting the growth and/or maintenance of a biofilm, the method comprising contacting the microorganism (or a biofilm comprising the microorganism) with a chimeric construct as described herein, or with an antimicrobial peptide as described herein, and/or with a composition comprising one or more isolated antimicrobial peptides as described herein. In certain embodiments the microorganism is a yeast or fungus and the chimeric construct or composition is a chimeric construct comprising an effector identified as killing a yeast or fungus, or a composition comprising an antimicrobial peptide described herein as killing a yeast or fungus. In certain embodiments the microorganism is a bacterium (e.g., gram negative and/or gram positive bacterium) and the chimeric construct or composition is a chimeric construct comprising an effector identified as killing a bacterium (e.g., gram negative and/or gram positive bacterium), or a composition comprising an antimicrobial peptide described herein as killing a gram negative and/or gram positive bacterium. In certain embodiments the effector is an antimicrobial peptide. In certain embodiments he microorganism is S. mutans, and the chimeric construct or composition is applied to the oral cavity of an animal or human, e.g., to reduces the incidence or severity of dental caries and/or periodontal disease). In certain embodiments the chimeric construct or composition preferentially targets Corynebacterium spp. and the chimeric construct or composition is applied to the skin surface of an animal or human (e.g., to reduce body odor).

Methods are also provided for disinfecting a surface. The methods typically involve contacting the surface with one or more chimeric constructs described herein, or a composition comprising one or more isolated antimicrobial peptides as described herein. In certain embodiments, the surface comprises a surface of a prosthesis or medical implant. In certain embodiments the surface comprises a surface of a medical device. In certain embodiments the surface comprises a surface of a plant or foodstuff. In certain embodiments the chimeric construct and/or the antimicrobial peptide(s) are combined with a second disinfectant selected from the group consisting of other antimicrobial agent is a disinfectant selected from the group consisting of acetic acid, phosphoric acid, citric acid, lactic, formic, propionic acid, hydrochloric acid, sulfuric acid, nitric acid, sodium hydroxide, potassium hydroxide, sodium carbonate, ammonium hydroxide, ethyl alcohol, isopropyl alcohol, phenol, formaldehyde, glutaraldehyde, hypochlorites, chlorine dioxide, sodium dichloroisocyanurate, chloramine-T, iodine, povidone-iodine, chlorhexidine, hydrogen peroxide, peracetic acid, and benzalkonium chloride.

In various embodiments the use of a chimeric construct described herein and/or an antimicrobial composition as described herein in the manufacture of a medicament for killing and/or inhibiting the growth and/or proliferation of a microorganism and/or inhibiting the growth and/or maintenance of a biofilm comprising the microorganism is provided. In certain embodiments the microorganism is a yeast or fungus and the chimeric construct or composition is a chimeric construct comprising an effector identified as killing a yeast or fungus, or a composition comprising an antimicrobial peptide described herein as killing a yeast or fungus. In certain embodiments the microorganism is a bacterium (e.g., gram negative and/or gram positive bacterium) and the chimeric construct or composition is a chimeric construct comprising an effector identified as killing a bacterium (e.g., gram negative and/or gram positive bacterium), or a composition comprising an antimicrobial peptide described herein as killing a gram negative and/or gram positive bacterium. In certain embodiments the effector is an antimicrobial peptide.

In various embodiments methods are also provided for of detecting a bacterium and/or a bacterial film (e.g., a biofilm comprising the bacteria). The methods typically involve contacting the bacterium or bacterial film with a composition comprising a detectable label attached to a targeting peptide comprising one or more amino acid sequences found Table 3 and/or Table 12; and detecting the detectable label where the quantity and/or location of the detectable label is an indicator of the presence of the bacterium and/or bacterial film. In certain embodiments the targeting peptide comprises or consists of an amino acid sequence of a peptide found in Table 3 (and/or the retro, inverso, retroinverso form of the sequence). In certain embodiments the detectable label is a label selected from the group consisting of a radioactive label, a radio-opaque label, a fluorescent dye, a fluorescent protein, an enzymatic label, a colorimetric label, and a quantum dot.

Certain compositions are also provided comprising a photosensitizing or photoactivatable agent attached to a targeting peptide (e.g., a peptide comprising an amino acid sequence of a peptide found in Table 3 and/or Table 12). In certain embodiments the targeting peptide comprises or consists of an amino acid sequence of a peptide found in Table 3. In certain embodiments the photosensitizing agent is an agent selected from the group consisting of a porphyrinic macrocycle, a porphyrin, a chlorine, a crown ether, an acridine, an azine, a phthalocyanine, a cyanine, a psoralen, a cucumin, and a perylenequinonoid. In certain embodiments the photosensitizing agent comprises one or more agents agent shown in any of FIGS. 1-12. In certain embodiments the photosensitizing agent is attached to the targeting peptide by a non-peptide linker (e.g., a polyethylene glycol (PEG)). In certain embodiments the photosensitizing agent is attached to the targeting peptide by a non-peptide linker found in Table 16.

In various embodiments methods are provided for killing and/or for inhibiting the growth and/or proliferation of a microorganism or a biofilm comprising a microorganism, where the methods involve contacting the microorganism or biofilm with a composition comprising a photosensitizing or photoactivatable agent attached to a targeting peptide (e.g., a peptide comprising an amino acid sequence of a peptide found in Table 3 and/or Table 12). In certain embodiments the targeting peptide comprises or consists of an amino acid sequence of a peptide found in Table 3. In certain embodiments the photosensitizing agent is an agent selected from the group consisting of a porphyrinic macrocycle, a porphyrin, a chlorine, a crown ether, an acridine, an azine, a phthalocyanine, a cyanine, a psoralen, a cucumin, and a perylenequinonoid. In certain embodiments the photosensitizing agent comprises one or more agents agent shown in any of FIGS. 1-12. In certain embodiments the photosensitizing agent is attached to the targeting peptide by a non-peptide linker (e.g., a polyethylene glycol (PEG)). In certain embodiments the photosensitizing agent is attached to the targeting peptide by a non-peptide linker found in Table 16. In certain embodiments the method further comprises exposing the microorganism or biofilm to a light source. In certain embodiments the microorganism is a microorganism selected from the group consisting of a bacterium (e.g., a gram positive and/or a gram negative bacterium), a yeast, a fungus, a protozoan, and a virus. In certain embodiments the biofilm comprises a bacterial film. In certain embodiments the biofilm is a biofilm on an implanted or implantable medical device. In certain embodiments the microorganism or biofilm is an organism or biofilm in an oral cavity.

In various embodiments certain formulations are provided. Typical formulations include, but are not limited to a targeting peptide, an antimicrobial peptide, and/or a STAMP; and a salt at a concentration comparable to that found in phosphate buffered saline (PBS) ranging from about 0.5×PBS to about 2.5×PBS. In certain embodiments the formulation comprises a targeting peptide found in Tables 3 or 10. In certain embodiments the formulation comprises an anti-S. mutans peptide targeting peptide (e.g., as identified in Tables 3 or 12). In certain embodiments the anti-S. mutans targeting peptide has the amino acid sequence TFFRLFNRSFTQALGK (SEQ ID NO:1). In certain embodiments the anti-S. mutans targeting peptide is attached to an antimicrobial peptide. In certain embodiments the antimicrobial peptide is a peptide found in Tables 4, 5, or 14. In certain embodiments the antimicrobial peptide has the amino acid sequence KNLRIIRKGIHIIKKY (SEQ ID NO:3080). In certain embodiments the formulation comprises the amino acid sequence of the C16G2 STAMP (TFFRLFNRSFTQALGKGGGKNLRIIRKGIHIIKKY, (SEQ ID NO:2). In various embodiments the targeting peptide, antimicrobial peptide, and/or a STAMP bears one or more protecting groups. In certain embodiments the protecting group(s) are independently selected from the group consisting of acetyl, amide, 3 to 20 carbon alkyl groups, Fmoc, Tboc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl), Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bom), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), and Trifluoroacetyl (TFA). In certain embodiments the targeting peptide, antimicrobial peptide, and/or a STAMP is amidated at the carboxyl terminus and/or bears an acetyl group at the amino terminus. In certain embodiments the pH of the formulation ranges from about pH 5.0 to about pH 8.5. In certain embodiments the pH is about pH 7.4. In various embodiments the salt is at a concentration comparable to that found in 1×PBS. In certain embodiments the formulation comprises PBS. In certain embodiments the formulation of further comprising ethanol, and/or glycerin, and/or polyethylene glycol, and/or fluoride.

DEFINITIONS

The term “peptide” as used herein refers to a polymer of amino acid residues typically ranging in length from 2 to about 50 or about 60 residues. In certain embodiments the peptide ranges in length from about 2, 3, 4, 5, 7, 9, 10, or 11 residues to about 60, 50, 45, 40, 45, 30, 25, 20, or 15 residues. In certain embodiments the peptide ranges in length from about 8, 9, 10, 11, or 12 residues to about 15, 20 or 25 residues. In certain embodiments the amino acid residues comprising the peptide are “L-form” amino acid residues, however, it is recognized that in various embodiments, “D” amino acids can be incorporated into the peptide. Peptides also include amino acid polymers in which one or more amino acid residues is an artificial chemical analogue of a corresponding naturally occurring amino acid, as well as to naturally occurring amino acid polymers. In addition, the term applies to amino acids joined by a peptide linkage or by other, “modified linkages” (e.g., where the peptide bond is replaced by an α-ester, a β-ester, a thioamide, phosphonamide, carbonate, hydroxylate, and the like (see, e.g., Spatola, (1983) Chem. Biochem. Amino Acids and Proteins 7: 267-357), where the amide is replaced with a saturated amine (see, e.g., Skiles et al., U.S. Pat. No. 4,496,542, which is incorporated herein by reference, and Kaltenbronn et al., (1990) Pp. 969-970 in Proc. 11th American Peptide Symposium, ESCOM Science Publishers, The Netherlands, and the like)).

The term “residue” as used herein refers to natural, synthetic, or modified amino acids. Various amino acid analogues include, but are not limited to 2-aminoadipic acid, 3-aminoadipic acid, beta-alanine (beta-aminopropionic acid), 2-aminobutyric acid, 4-aminobutyric acid, piperidinic acid, 6-aminocaproic acid, 2-aminoheptanoic acid, 2-aminoisobutyric acid, 3-aminoisobutyric acid, 2-aminopimelic acid, 2,4 diaminobutyric acid, desmosine, 2,2′-diaminopimelic acid, 2,3-diaminopropionic acid, n-ethylglycine, n-ethylasparagine, hydroxylysine, allo-hydroxylysine, 3-hydroxyproline, 4-hydroxyproline, isodesmosine, allo-isoleucine, n-methylglycine, sarcosine, n-methylisoleucine, 6-n-methyllysine, n-methylvaline, norvaline, norleucine, ornithine, and the like. These modified amino acids are illustrative and not intended to be limiting.

“β-peptides” comprise of “β amino acids”, which have their amino group bonded to the β carbon rather than the α-carbon as in the 20 standard biological amino acids. The only commonly naturally occurring β amino acid is β-alanine.

Peptoids, or N-substituted glycines, are a specific subclass of peptidomimetics. They are closely related to their natural peptide counterparts, but differ chemically in that their side chains are appended to nitrogen atoms along the molecule's backbone, rather than to the α-carbons (as they are in natural amino acids).

The terms “conventional” and “natural” as applied to peptides herein refer to peptides, constructed only from the naturally-occurring amino acids: Ala, Cys, Asp, Glu, Glu, Phe, Gly, His, Ile, Lys, Leu, Met, Asn, Pro, Gln, Arg, Ser, Thr, Val, Trp, and Tyr. A compound of the invention “corresponds” to a natural peptide if it elicits a biological activity (e.g., antimicrobial activity) related to the biological activity and/or specificity of the naturally occurring peptide. The elicited activity may be the same as, greater than or less than that of the natural peptide. In general, such a peptoid will have an essentially corresponding monomer sequence, where a natural amino acid is replaced by an N-substituted glycine derivative, if the N-substituted glycine derivative resembles the original amino acid in hydrophilicity, hydrophobicity, polarity, etc. The following are illustrative, but non-limiting N-substituted glycine replacements: N-(1-methylprop-1-yl)glycine substituted for isoleucine (Ile), N-(prop-2-yl)glycine for valine (Val), N-benzylglycine for phenylanlaine (Phe), N-(2-hydroxyethyl)glycine for serine (Ser), and the like. In certain embodiments substitutions need not be “exact”. Thus for example, in certain embodiments N-(2-hydroxyethyl)glycine may substitute for Ser, Thr, Cys, and/or Met; N-(2-methylprop-1-yl)glycine may substitute for Val, Leu, and/or Ile. In certain embodiments N-(2-hydroxyethyl)glycine can be used to substitute for Thr and Ser, despite the structural differences: the side chain in N-(2-hydroxyethyl)glycine is one methylene group longer than that of Ser, and differs from Thr in the site of hydroxy-substitution. In general, one may use an N-hydroxyalkyl-substituted glycine to substitute for any polar amino acid, an N-benzyl- or N-aralkyl-substituted glycine to replace any aromatic amino acid (e.g., Phe, Trp, etc.), an N-alkyl-substituted glycine such as N-butylglycine to replace any nonpolar amino acid (e.g., Leu, Val, Ile, etc.), and an N-(aminoalkyl)glycine derivative to replace any basic polar amino acid (e.g., Lys and Arg).

Where an amino acid sequence is provided herein, L-, D-, or beta amino acid versions of the sequence are also contemplated as well as retro, inversion, and retro-inversion isoforms. In addition, conservative substitutions (e.g., in the binding peptide, and/or antimicrobial peptide, and/or linker peptide) are contemplated. Non-protein backbones, such as PEG, alkane, ethylene bridged, ester backbones, and other backbones are also contemplated. Also fragments ranging in length from about 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, or 25 amino acids up to the full length minus one amino acid of the peptide are contemplated where the fragment retains at least 50%, preferably at least 60% 70% or 80%, more preferably at least 90%, 95%, 98%, 99%, or at least 100% of the activity (e.g., binding specificity and/or avidity, antimicrobial activity, etc.) of the full length peptide are contemplated.

A “compound antimicrobial peptide” or “compound AMP” refers to a construct comprising two or more AMPs joined together. The AMPs can be joined directly or through a linker. They can be chemically conjugated or, where joined directly together or through a peptide linker can comprise a fusion protein.

In certain embodiments, conservative substitutions of the amino acids comprising any of the sequences described herein are contemplated. In various embodiments one, two, three, four, or five different residues are substituted. The term “conservative substitution” is used to reflect amino acid substitutions that do not substantially alter the activity (e.g., antimicrobial activity and/or specificity) of the molecule. Typically conservative amino acid substitutions involve substitution one amino acid for another amino acid with similar chemical properties (e.g. charge or hydrophobicity). Certain conservative substitutions include “analog substitutions” where a standard amino acid is replaced by a non-standard (e.g., rare, synthetic, etc) amino acid differing minimally from the parental residue. Amino acid analogs are considered to be derived synthetically from the standard amino acids without sufficient change to the structure of the parent, are isomers, or are metabolite precursors. Examples of such “analog substitutions” include, but are not limited to, 1) Lys-Orn, 2) Leu-Norleucine, 3) Lys-Lys[TFA], 4) Phe-Phe[Gly], and 5) δ-amino butylglycine-ξ-amino hexylglycine, where Phe[gly] refers to phenylglycine (a Phe derivative with a H rather than CH₃ component in the R group), and Lys[TFA] refers to a Lys where a negatively charged ion (e.g., TFA) is attached to the amine R group. Other conservative substitutions include “functional substitutions” where the general chemistries of the two residues are similar, and can be sufficient to mimic or partially recover the function of the native peptide. Strong functional substitutions include, but are not limited to 1) Gly/Ala, 2) Arg/Lys, 3) Ser/Tyr/Thr, 4) Leu/Ile/Val, 5) Asp/Glu, 6) Gln/Asn, and 7) Phe/Trp/Tyr, while other functional substitutions include, but are not limited to 8) Gly/Ala/Pro, 9) Tyr/His, 10) Arg/Lys/His, 11) Ser/Thr/Cys, 12) Leu/Ile/Val/Met, and 13) Met/Lys (special case under hydrophobic conditions). Various “broad conservative substations” include substitutions where amino acids replace other amino acids from the same biochemical or biophysical grouping. This is similarity at a basic level and stems from efforts to classify the original 20 natural amino acids. Such substitutions include 1) nonpolar side chains: Gly/Ala/Val/Leu/Ile/Met/Pro/Phe/Trp, and/or 2) uncharged polar side chains Ser/Thr/Asn/Gln/Tyr/Cys. In certain embodiments broad-level substitutions can also occur as paired substitutions. For example, Any hydrophilic neutral pair [Ser, Thr, Gln, Asn, Tyr, Cys]+[Ser, Thr, Gln, Asn, Tyr, Cys] can may be replaced by a charge-neutral charged pair [Arg, Lys, His]+[Asp, Glu]. The following six groups each contain amino acids that, in certain embodiments, are typical conservative substitutions for one another: 1) Alanine (A), Serine (S), Threonine (T); 2) Aspartic acid (D), Glutamic acid (E); 3) Asparagine (N), Glutamine (Q); 4) Arginine (R), Lysine (K), Histidine (H); 5) Isoleucine (I), Leucine (L), Methionine (M), Valine (V); and 6) Phenylalanine (F), Tyrosine (Y), Tryptophan (W). Where amino acid sequences are disclosed herein, amino acid sequences comprising, one or more of the above-identified conservative substitutions are also contemplated.

In certain embodiments, targeting peptides, antimicrobial peptides, and/or STAMPs compromising at least 80%, preferably at least 85% or 90%, and more preferably at least 95% or 98% sequence identity with any of the sequences described herein are also contemplated. The terms “identical” or percent “identity,” refer to two or more sequences that are the same or have a specified percentage of amino acid residues that are the same, when compared and aligned for maximum correspondence, as measured using one of the following sequence comparison algorithms or by visual inspection. With respect to the peptides of this invention sequence identity is determined over the full length of the peptide. For sequence comparison, typically one sequence acts as a reference sequence, to which test sequences are compared. When using a sequence comparison algorithm, test and reference sequences are input into a computer, subsequence coordinates are designated, if necessary, and sequence algorithm program parameters are designated. The sequence comparison algorithm then calculates the percent sequence identity for the test sequence(s) relative to the reference sequence, based on the designated program parameters. Optimal alignment of sequences for comparison can be conducted, e.g., by the local homology algorithm of Smith & Waterman (1981) Adv. Appl. Math. 2: 482, by the homology alignment algorithm of Needleman & Wunsch (1970) J. Mol. Biol. 48: 443, by the search for similarity method of Pearson & Lipman (1988) Proc. Natl. Acad. Sci., USA, 85: 2444, by computerized implementations of these algorithms (GAP, BESTFIT, FASTA, and TFASTA in the Wisconsin Genetics Software Package, Genetics Computer Group, 575 Science Dr., Madison, Wis.), or by visual inspection.

The term “specificity” when used with respect to the antimicrobial activity of a peptide indicates that the peptide preferentially inhibits growth and/or proliferation and/or kills a particular microbial species as compared to other related and/or unrelated microbes. In certain embodiments the preferential inhibition or killing is at least 10% greater (e.g., LD₅₀ is 10% lower), preferably at least 20%, 30%, 40%, or 50%, more preferably at least 2-fold, at least 5-fold, or at least 10-fold greater for the target species.

“Treating” or “treatment” of a condition as used herein may refer to preventing the condition, slowing the onset or rate of development of the condition, reducing the risk of developing the condition, preventing or delaying the development of symptoms associated with the condition, reducing or ending symptoms associated with the condition, generating a complete or partial regression of the condition, or some combination thereof.

The term “consisting essentially of” when used with respect to an antimicrobial peptide (AMP) or AMP motif as described herein, indicates that the peptide or peptides encompassed by the library or variants, analogues, or derivatives thereof possess substantially the same or greater antimicrobial activity and/or specificity as the referenced peptide. In certain embodiments substantially the same or greater antimicrobial activity indicates at least 80%, preferably at least 90%, and more preferably at least 95% of the anti microbial activity of the referenced peptide(s) against a particular bacterial species (e.g., S. mutans).

The term “porphyrinic macrocycle” refers to a porphyrin or porphyrin derivative. Such derivatives include porphyrins with extra rings ortho-fused, or orthoperifused, to the porphyrin nucleus, porphyrins having a replacement of one or more carbon atoms of the porphyrin ring by an atom of another element (skeletal replacement), derivatives having a replacement of a nitrogen atom of the porphyrin ring by an atom of another element (skeletal replacement of nitrogen), derivatives having substituents other than hydrogen located at the peripheral (meso-, .beta.-) or core atoms of the porphyrin, derivatives with saturation of one or more bonds of the porphyrin (hydroporphyrins, e.g., chlorins, bacteriochlorins, isobacteriochlorins, decahydroporphyrins, corphins, pyrrocorphins, etc.), derivatives obtained by coordination of one or more metals to one or more porphyrin atoms (metalloporphyrins), derivatives having one or more atoms, including pyrrolic and pyrromethenyl units, inserted in the porphyrin ring (expanded porphyrins), derivatives having one or more groups removed from the porphyrin ring (contracted porphyrins, e.g., corrin, corrole) and combinations of the foregoing derivatives (e.g. phthalocyanines, porphyrazines, naphthalocyanines, subphthalocyanines, and porphyrin isomers). Certain porphyrinic macrocycles comprise at least one 5-membered ring.

As used herein, an “antibody” refers to a protein consisting of one or more polypeptides substantially encoded by immunoglobulin genes or fragments of immunoglobulin genes. The recognized immunoglobulin genes include the kappa, lambda, alpha, gamma, delta, epsilon and mu constant region genes, as well as myriad immunoglobulin variable region genes. Light chains are classified as either kappa or lambda. Heavy chains are classified as gamma, mu, alpha, delta, or epsilon, which in turn define the immunoglobulin classes, IgG, IgM, IgA, IgD and IgE, respectively.

A typical immunoglobulin (antibody) structural unit is known to comprise a tetramer. Each tetramer is composed of two identical pairs of polypeptide chains, each pair having one “light” (about 25 kD) and one “heavy” chain (about 50-70 kD). The N-terminus of each chain defines a variable region of about 100 to 110 or more amino acids primarily responsible for antigen recognition. The terms variable light chain (V_(L)) and variable heavy chain (V_(H)) refer to these light and heavy chains respectively.

Antibodies exist as intact immunoglobulins or as a number of well characterized fragments produced by digestion with various peptidases. Thus, for example, pepsin digests an antibody below the disulfide linkages in the hinge region to produce F(ab)′₂, a dimer of Fab which itself is a light chain joined to V_(H)-C_(H)1 by a disulfide bond. The F(ab)′₂ may be reduced under mild conditions to break the disulfide linkage in the hinge region thereby converting the (Fab′)₂ dimer into an Fab′ monomer. The Fab′ monomer is essentially an Fab with part of the hinge region (see, Fundamental Immunology, W. E. Paul, ed., Raven Press, N.Y. (1993), for a more detailed description of other antibody fragments). While various antibody fragments are defined in terms of the digestion of an intact antibody, one of skill will appreciate that such Fab′ fragments may be synthesized de novo either chemically or by utilizing recombinant DNA methodology. Thus, the term antibody, as used herein also includes antibody fragments either produced by the modification of whole antibodies or synthesized de novo using recombinant DNA methodologies, including, but are not limited to, Fab′₂, IgG, IgM, IgA, scFv, dAb, nanobodies, unibodies, and diabodies.

In certain embodiments antibodies and fragments of the present invention can be bispecific. Bispecific antibodies or fragments can be of several configurations. For example, bispecific antibodies may resemble single antibodies (or antibody fragments) but have two different antigen binding sites (variable regions). In various embodiments bispecific antibodies can be produced by chemical techniques (Kranz et al. (1981) Proc. Natl. Acad. Sci., USA, 78: 5807), by “polydoma” techniques (see, e.g., U.S. Pat. No. 4,474,893), or by recombinant DNA techniques. In certain embodiments bispecific antibodies of the present invention can have binding specificities for at least two different epitopes, at least one of which is an epitope of a microbial organism. The microbial binding antibodies and fragments can also be heteroantibodies. Heteroantibodies are two or more antibodies, or antibody binding fragments (e.g., Fab) linked together, each antibody or fragment having a different specificity.

The term “STAMP” refers to Specifically Targeted Anti-Microbial Peptides. In various embodiments, a STAMP comprises one or more peptide targeting moieties attached to one or more antimicrobial moieties (e.g., antimicrobial peptides (AMPs)). An MH-STAMP is a STAMP bearing two or more targeting domains (i.e., a multi-headed STAMP).

The terms “isolated” “purified” or “biologically pure” refer to material which is substantially or essentially free from components that normally accompany it as found in its native state. In the case of a peptide, an isolated (naturally occurring) peptide is typically substantially free of components with which it is associated in the cell, tissue, or organism. The term isolated also indicates that the peptide is not present in a phage display, yeast display, or other peptide library.

In various embodiments the amino acid abbreviations shown in Table 1 are used herein.

TABLE 1 Amino acid abbreviations. Abbreviation Name 3 Letter 1 Letter Alanine Ala A βAlanine (NH₂-CH₂-CH₂-COOH) βAla Arginine Arg R Asparagine Asn N Aspartic Acid Asp D Cysteine Cys C Glutamic Acid Glu E Glutamine Gln Q Glycine Gly G Histidine His H Homoserine Hse — Isoleucine Ile I Leucine Leu L Lysine Lys K Methionine Met M Methionine sulfoxide Met (O) — Methionine methylsulfonium Met (S-Me) — Norleucine Nle — Phenylalanine Phe F Proline Pro P Serine Ser S Threonine Thr T Tryptophan Trp W Tyrosine Tyr Y Valine Val V episilon-aminocaproic acid Ahx J (NH²-(CH₂)₅-COOH) 4-aminobutanoic acid gAbu (NH²-(CH₂)₃-COOH) tetrahydroisoquinoline-3- O carboxylic acid Lys(N(epsilon)-trifluoroacetyl) K[TFA] α-aminoisobutyric acid Aib B

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows some illustrative porphyrins (compounds 92-99) suitable for use as targeting moieties and/or antimicrobial effectors.

FIG. 2 shows some illustrative porphyrins (compounds 100-118) suitable for use as targeting moieties and/or antimicrobial effectors.

FIG. 3 shows some illustrative porphyrins (in particular phthalocyanines) (compounds 119-128) suitable for use as targeting moieties and/or antimicrobial effectors.

FIG. 4 illustrates the structures of two phthalocyanines, Monoastral Fast Blue B and Monoastral Fast Blue G suitable for use as targeting moieties and/or antimicrobial effectors.

FIG. 5 illustrates certain azine photosensitizers suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 6 shows illustrative cyanine suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 7 shows illustrative psoralen (angelicin) photosensitizers suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 8 shows illustrative hypericin and the perylenequinonoid pigments suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 9 shows illustrative acridines suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 10 illustrates the structure of the acridine Rose Bengal.

FIG. 11 illustrates various crown ethers suitable for use as targeting moieties and/or antimicrobial effectors in the compositions and methods described herein.

FIG. 12 illustrates the structure of cumin.

FIG. 13 illustrates an example of a targeted light-activated porphyrin we have constructed: C16-P18 comprising a porphyrin coupled to a C16 (SEQ ID NO:3) targeting sequence.

FIG. 14 schematically shows some illustrative configurations for chimeric constructs described herein. A: Shows a single targeting moiety T1 attached to a single effector E1 by a linker/spacer L. B: Shows multiple targeting moieties T1, T2, T3 attached directly to each other and attached by a linker L to a single effector E1. In various embodiments T1, T2, and T3, can be domains in a fusion protein. C: Shows multiple targeting moieties T1, T2, T3 attached to each other by linkers L and attached by a linker L to a single effector E1. In various embodiments T1, T2, and T3, can be domains in a fusion protein. D: Shows a single targeting moiety T1 attached by a linker L to multiple effectors E1, E2, and E3 joined directly to each other. E: Shows a single targeting moiety T1 attached by a linker L to multiple effectors E1, E2, and E3 joined to each other by linkers L. F: Shows multiple targeting moieties joined directly to each other and by a linker L to multiple effectors joined to each other by linkers L. G: Shows multiple targeting moieties joined to each other by linkers L and by a linker L to multiple effectors joined to each other by linkers L. In various embodiments T1, T2, and T3, and/or E1, E2, and E3 can be domains in a fusion protein. H: Illustrates a branched configuration where multiple targeting moieties are linked to a single effector. I: Illustrates a dual branched configuration where multiple targeting moieties are linked to multiple effectors. J: Illustrates a branched configuration where multiple targeting moieties are linked to multiple effectors where the effectors are joined to each other in a linear configuration.

FIG. 15 illustrates various MH-STAMPs used in Example 1. The design, sequence, and observed mass (m/z) for M8(KH)-20 (SEQ ID NOs:4, 5, and 6), BL(KH)-20 (SEQ ID 7, 8, and 9), and M8(BL)-20 (SEQ ID 10, 11, and 12).

FIGS. 16A and 16B show HPLC and MS spectra of M8(KH)-20. The quality of the completed MH-STAMP was analyzed by HPLC (FIG. 16A) and MALDI mass spectroscopy (FIG. 16B). At UV absorbance 215 nm (260 and 280 nm are also plotted), a single major product was detected by HPLC (* retention volume 11.04 mL). After fraction collection, the correct mass (m/z) for single-charged M8(KH)-20, 4884.91 (marked by *), was observed for this peak. Y-axis: 16A, mAU miliabsorbance units; 16B, percent intensity.

FIG. 17A-17E show growth inhibitory activity of MH-STAMPs. Monocultures of S. mutans (FIG. 17A); P. aeruginosa (FIG. 17B); S. epidermidis (FIG. 17C); S. aureus (FIG. 17D); or E. coli (FIG. 17E); were treated with peptides (as indicated in the figure) for 10 min. Agent was then removed and fresh media returned. Culture recovery was measured over time (OD600). Plots represent the average of at least 3 independent experiments with standard deviations.

FIG. 18 illustrates the selective activity of dual-targeted and single-targeted MH-STAMPs in mixed culture. A mixture of P. aeruginosa (Pa), S. mutans (Sm), E. coli (Ec), and S. epidermidis (Se) planktonic cells were mixed with MH-STAMPs (as indicated in the figure) and treated 24 h. After incubation, cfu/mL of remaining constituent species were quantitated after plating to selective media. * indicates under 200 surviving cfu/mL recovered.

FIGS. 19A and 19B illustrate Rose Bengal (FIG. 19A) and synthesis scheme for C16-RB, halides and side-chains omitted for clarity (FIG. 19B).

FIG. 20 shows LC/MS profile C16-RB. Purity and molecular mass of C16-RB was confirmed by LC/MS. A single product was observed at 11.92 min with mass species at 1040.8 and 1560.25 daltons. Expected C16-RB mas: m/z=3118, m²⁺/z=1559, m³⁺/z=1039.

FIG. 21 illustrates activity of RB and C16-RB against single-species S. mutans biofilms. * indicates fewer than 100 cfu/mL recovered

FIG. 22 shows S. mutans-specific C16-RB activity. C16-RB, and not RB alone, preferentially eliminated S. mutans, and not other oral streptococci, after blue light illumination.

DETAILED DESCRIPTION

In various embodiments, novel “targeting” peptides are identified that specifically or preferentially bind particular microorganisms (e.g., bacteria, yeasts, fungi, etc.). These peptides can be used alone to bind/capture and thereby identify and/or isolate particular target microorganisms, or they can be attached to one or more effectors (e.g., drugs, labels, etc.) and used as targeting moieties thereby providing a chimeric moiety that preferentially or specifically delivers the effector to a target microorganism, a population of target microorganisms, a microbial film, a biofilm, and the like.

In various embodiments novel peptides having antimicrobial activity against certain bacteria, fungi, yeasts, and/or viruses and/or having activity that inhibits the growth or maintenance of biofilms comprising such microorganisms are provided. The AMPs can be used to inhibit the growth and/or proliferation of a microbial species and/or the growth and/formation and/or maintenance of a biofilm comprising the microbial species.

In certain embodiments, the targeting moieties can be attached to antimicrobial peptides to form Specifically Targeted Anti-Microbial Peptides (STAMPs). In certain embodiments attachment of one or more targeting moieties/peptides to one or more antimicrobial peptides can narrow the spectrum of activity of the AMP(s) to provide efficacy against one or a few target microorganisms without substantially disrupting the remaining microbial ecology and thereby provide increased efficacy with fewer side effects.

In certain embodiments STAMPs or effector peptides can be delivered against pathogenic bacteria by being cloned and expressed in probiotic organisms for therapeutic delivery in vivo. Recombinant expression (and overexpression) and export of antimicrobial peptides and other peptides are well documented in bacteria, including species that are also utilized as probiotics.

In various embodiments the targeting peptides, antimicrobial peptides, and/or STAMPs can be formulated individually, in combination with each other, in combination with other antimicrobial peptides, and/or in combination with various antibacterial agents to provide antimicrobial reagents and/or pharmaceuticals.

Accordingly, in certain embodiments this invention provides peptides having antimicrobial activity, compositions comprising the peptides, methods of using the peptides (or compositions thereof) to inhibit the growth of or kill a wide variety of microbial targets and methods of using the peptides (or compositions thereof) to treat or prevent microbial infections and diseases related thereto in both plants and animals.

The various peptides (targeting peptides, AMPs, STAMPs, etc.) described herein exhibit antimicrobial activity, being biostatic or biocidal against a certain microbial targets, including but not limited to, Gram-negative bacteria such as Acinetobacter baumannii, Escherichia coli, Fusobacterium nucleatum, Pseudomonas aeruginosa, Porphyromonas gingivalis; Gram-positive bacteria such as Actinomyces naeslundii, Bacillus subtilis, Clostridium difficile, Enterococcus faecalis, Staphylococcus aureus (and MRSA), S. epidermidis, Streptococcus mutans, Streptococcus pneumoniae; and yeast or fungi such as Aspergillus niger, Candida albicans, Malassezia furfur, and Trichophyton rubrum (see, e.g., Table 2). Significantly, various peptides described herein are biostatic or biocidal against clinically relevant pathogens exhibiting multi-drug resistance such as, for example, methicillin-resistant Staphylococcus aureus (“MRSA”).

TABLE 2 Illustrative target microorganisms and associated pathology. Acinetobacter baumannii Pathogenic gram-negative bacillus that is naturally sensitive (A. baumannii) to relatively few antibiotics. Actinomyces naeslundii Gram positive rod shaped bacteria that occupy the oral (A. naeslundii) cavity and are implicated in periodontal disease and root caries. Aspergillus niger A fungal infection that often causes a black mould to appear (A. niger) on some fruit and vegetables but may also infect humans through inhalation of fungal spores. Bacteroides fragilis Gram positive bacilli that are opportunistic human pathogens, (B. fragilis) causing infections of the peritoneal cavity, gastrointestinal surgery, and appendicitis via abscess formation, inhibiting phagocytosis. Resistant to a wide variety of antibiotics— β-lactams, aminoglycosides, and recently many species have acquired resistance to erythromycin and tetracycline. Bacillus subtilis Gram-positive, catalase-positive bacterium. (B. subtilis) Candida albicans Causal agent of opportunistic oral and genital fungal infections (C. albicans) in humans. Clostridium difficile A gram-positive, anaerobic, spore-forming bacillus that is (C. difficile) responsible for the development of antibiotic-associated diarrhea and colitis. Corynebacterium jeikeium Gram positive, opportunistic pathogen primarily of (C. jeikeium) immunocompromised (neutropenic) patients. Highly resistant to antibiotics Campylobacter jejuni Gram negative cause of human gastroenteritis/food poisoning. (C. jejuni) Escherichia coli Gram negative rod-shaped bacterium commonly found in the (E. coli) lower intestine of warm-blooded organisms. Certain strains cause serious food poisoning in humans. Enterococcus faecalis Gram-positive commensal bacterium (E. faecalis) Fusobacterium nucleatum Gram negative schizomycetes bacterium often seen in necrotic (F. nucleatum) tissue and implicated, but not conclusively, with other organisms in the causation and perpetuation of periodontal disease. Lactobacillus acidophilus Gram-positive commensal bacterium. (L. acidophilus) Legionella pneumophila Gram negative bacterium that is the causative agent of (L. pneumophila) legionellosis or Legionnaires' disease. (Micrococcus luteus) Gram positive, spherical, saprotrophic bacterium found in M. luteus soil, dust, water and air, and as part of the normal flora of the mammalian skin. The bacterium also colonizes the human mouth, mucosae, oropharynx and upper respiratory tract. Considered an emerging nosocomial pathogen in immunocompromised patients. Mycobacterium Gram-variable (acid-fast) soil-dwelling organism utilized as smegmatis a proxy for Mycobacterium tuberculosis during research and (M. smegmatis) development. Malassezia furfur Yeast—cutaneous pathogen. (M. furfur) Methicillin-resistant Any strain of Staphylococcus aureus bacteria (gram positive) Staphylococcus aureus that is resistant to a one or more members of a large group of (MRSA) antibiotics called the beta-lactams. Responsible for skin and systemic infections. Myxococcus xanthus Gram negative cells that form biofilms and display primitive (M. xanthus) social motility and fruiting body organization. Pseudomonas aeruginosa Gram-negative rod. Frequent opportunistic pathogen and P. aeruginosa infects burn wounds. Causes ear infections in children. Infects the lungs of cystic fibrosis patients. Porphyromonas gingivalis Non-motile, gram-negative, rod-shaped, anaerobic (P. gingivalis) pathogenic bacterium (periodontal disease) Progeussmirabilis Gram-negative, facultatively anaerobic bacterium. Causes (P. mirabilis) 90% of all ‘Proteus’ infections in humans. S. epidermidis Gram-positive, coagulase-negative cocci. Nosocomial (S. epidermidis) pathogen associated with infection (biofilm) of implanted medical device. Streptococcus mutans Gram-positive, facultatively anaerobic bacterium commonly (S. mutans) found in the human oral cavity and is a significant contributor to tooth decay Streptococcus Gram-positive, alpha-hemolytic, bile soluble aerotolerant pneumoniae anaerobe. Causal agent for streptococcal pneumonia. (S. pneumoniae) Treponema denticola Gram-negative oral spirochete associated with the incidence (T. denticola) and severity of human periodontal disease. Trichophyton rubrum Most common cause of athlete's foot, jock itch and ringworm. (T. rubrum)

The various agents described herein (targeting peptides, compound targeting peptides, antimicrobial peptides (AMPs) and/or compound AMPs, STAMPs and/or other chimeric moieties). or compositions thereof, are useful as biocidal or biostatic or fungicidal or fungistatic agents and/or virucidal agents in a wide variety of applications. For example, the agents can be used to disinfect or preserve a variety of materials including medical instruments, foodstuffs, medicaments, cosmetics and other nutrient-containing materials. Various peptides described herein are particularly useful as bacteriostatic or bactericidal agents against multi-drug-resistant pathogens such as MRSA in a variety of clinical settings.

The agents described herein, or compositions thereof, are also useful for the prophylaxis or treatment of microbial infections and diseases related thereto in both plants and animals. Such diseases include, but are not limited to, Gram-negative and Gram-positive bacterial infections, endocarditis, pneumonia and other respiratory infections, urinary tract infections, systemic candidiasis, oral mucositis, fungal infections, biofilm formation or maintenance (e.g., on medical implants), and the like.

In various embodiments, the agents described herein can be formulated individually, in combination with each other, in combination with other antimicrobial peptides, and/or in combination with various antibiotic (e.g., antibacterial) agents in “home healthcare” formulations. Such formulations include, but are not limited to toothpaste, mouthwash, tooth whitening strips or solutions, contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasal application, wound dressings (e.g., bandages), and the like.

Such applications are illustrative and not limiting. Using the teachings provided herein other uses of the AMPs and compositions described herein will be recognized by one of

I. Targeting Peptides.

A) Uses of Targeting Peptides.

The novel microorganism-binding peptides (targeting peptides) described herein can be used to preferentially or specifically deliver an effector to a microorganism (e.g., a bacterium, a fungus, a protozoan, an algae, etc.), to a bacterial film, to a biofilm, and the like. The targeting peptides described herein can be used to bind to and thereby label particular targets, and/or as capture reagents to bind target microorganisms and thereby provide an indicator of the presence and/or quantity of the target microorganism(s). In certain embodiments the targeting peptide can be attached to an effector such as an epitope tag and/or a detectable label and thereby facilitate the identification of the presence and/or location, and/or quantity of the target (e.g., target organism). Thus targeting moieties are thus readily adapted for use in in vivo diagnostics, and/or ex vivo assays. Moreover, because of small size and good stability, microorganism binding peptides are well suited for microassay systems (e.g., microfluidic assays (Lab on a Chip), microarray assays, and the like).

In certain embodiments the microorganism binding peptides (targeting peptides) can be attached to an effector that has antimicrobial activity (e.g., an antimicrobial peptide, an antibacterial and/or antifungal, a vehicle that contains an antibacterial or antifungal, etc. In various embodiments these chimeric moieties can be used in vivo, or ex vivo to preferentially inhibit or kill the target organism(s).

In certain embodiments the targeting peptides can be recombinantly expressed as part of a yeast or phage tail fiber or coat protein to enhance binding of the yeast or phage to a specific bacterial Gram-designation, genus, species, or strain. Phage with expressed peptides will then display altered infection selectivity towards a designed target bacteria for use in phage therapy. Cloning the DNA encoding a peptide of interest into the major or minor coat proteins of a bacteriophage, for example in Proteins I through VIII of phages SAP-2, M13, or T7, will result in a targeted phage expressing 1-200 copies of the targeting peptide on the phage surface.

In certain embodiments the targeting peptides can be used in various pre-targeting protocols. In pre-targeting protocols, a chimeric molecule is utilized comprising a primary targeting species (e.g. a microorganism-binding peptide) that specifically binds the desired target (e.g. a bacterium) and an effector that provides a binding site that is available for binding by a subsequently administered second targeting species. Once sufficient accretion of the primary targeting species (the chimeric molecule) is achieved, a second targeting species comprising (i) a diagnostic or therapeutic agent and (ii) a second targeting moiety, that recognizes the available binding site of the primary targeting species, is administered.

An illustrative example of a pre-targeting protocol is the biotin-avidin system for administering a cytotoxic radionuclide to a tumor. In a typical procedure, a monoclonal antibody targeted against a tumor-associated antigen is conjugated to avidin and administered to a patient who has a tumor recognized by the antibody. Then the therapeutic agent, e.g., a chelated radionuclide covalently bound to biotin, is administered. The radionuclide, via its attached biotin is taken up by the antibody-avidin conjugate pretargeted at the tumor. Examples of pre-targeting biotin/avidin protocols are described, for example, in Goodwin et al., U.S. Pat. No. 4,863,713; Goodwin et al. (1988) J. Nucl. Med. 29: 226; Hnatowich et al. (1987) J. Nucl. Med. 28: 1294; Oehr et al. (1988) J. Nucl. Med. 29: 728; Klibanov et al. (1988) J. Nucl. Med. 29: 1951; Sinitsyn et al. (1989) J. Nucl. Med. 30: 66; Kalofonos et al. (1990) J. Nucl. Med. 31: 1791; Schechter et al. (1991) Int. J. Cancer 48:167; Paganelli et al. (1991) Cancer Res. 51: 5960; Paganelli et al. (1991) Nucl. Med. Commun. 12: 211; Stickney et al. (1991) Cancer Res. 51: 6650; and Yuan et al. (1991) Cancer Res. 51:3119.

It will be recognized that the tumor-specific antibody used for cancer treatments can be replaced with a microorganism binding peptide of the present invention and similar pre-targeting strategies can be used to direct labels, antibiotics, and the like to the target organism(s).

Three-step pre-targeting protocols in which a clearing agent is administered after the first targeting composition has localized at the target site also have been described. The clearing agent binds and removes circulating primary conjugate which is not bound at the target site, and prevents circulating primary targeting species (antibody-avidin or conjugate, for example) from interfering with the targeting of active agent species (biotin-active agent conjugate) at the target site by competing for the binding sites on the active agent-conjugate. When antibody-avidin is used as the primary targeting moiety, excess circulating conjugate can be cleared by injecting a biotinylated polymer such as biotinylated human serum albumin. This type of agent forms a high molecular weight species with the circulating avidin-antibody conjugate which is quickly recognized by the hepatobiliary system and deposited primarily in the liver.

Examples of these protocols are disclosed, e.g., in PCT Application No. WO 93/25240; Paganelli et al. (1991) Nucl. Med. Comm., 12: 211-234; Oehr et al. (1988) J. Nucl. Med., 29: 728-729; Kalofonos et al. (1990) J. Nucl. Med., 31: 1791-1796; Goodwin et al. (1988) J. Nucl. Med., 29: 226-234; and the like).

These applications of microorganism binding peptides of this invention are intended to be illustrative and not limiting. Using the teaching provided herein, other uses will be recognized by one of skill in the art.

B) Illustrative Novel Targeting Peptides.

In certain embodiments, the targeting moiety comprises one or more targeting peptides that bind particular bacteria, fungi, and/or yeasts, and/or algae, and/or viruses and/or that bind particular groups of bacteria, and/or groups of fungi, and/or groups of yeasts, and/or groups of algae.

In certain embodiments the targeting peptides include peptides comprising or consisting of one or more of the amino acid sequences shown in Table 3 (SEQ ID NOs:13-1566). In various embodiments the peptides include peptides comprising or consisting of the retro, inverso, retro-inverso, and/or beta form of one or more of the amino acid sequences shown in Table 3. Also contemplated are circular permutations of these sequences as well as peptides comprising or consisting of the retro, inverso, retro-inverso, and/or beta form of such circular permutations.

It will also be recognized, that in certain embodiments, any peptide or compound AMP described herein can be circularized.

In various embodiments the peptides can optionally bear one or more protecting groups, e.g., and the amino and/or carboxyl termini, and/or on side chains.

Also contemplated are peptides comprising one, two, three four, or five conservative substitutions of these amino acid sequences.

TABLE 3 Illustrative list of novel targeting peptides. SEQ ID ID Target(s) Targeting Peptide Sequence NO 1T-3 S. mutans VLGIAGGLDAYGELVGGN 13 S. gordonii 1T-4 S. mutans LDAYGELVGGN 14 S. gordonii S. sanguinis S. oxalis V. atypica L. casei 1T-6 S. mutans KFINGVLSQFVLERK 15 1T-7 M. xanthus SQRIIEPVKSPQPYPGFSVS 16 1T-8 M. xanthus FSVAACGEQRAVTFVLLIEDLI 17 1T-9 M. xanthus WAWAESPRCVSTRSNIHALAFRVEVAA 18 LT 1T-10 M. xanthus SPAGLPGDGDEA 19 1T-11 S. mutans RISE 20 S. epidermidis P. aeruginosa 1T-12 C. xerosis FGNIFKGLKDVIETIVKWTAAK 21 C. striatum S. epidermidis S. mutans 1T-13 S. aureus FRSPCINNNSLQPPGVYPAR 22 S. epidermidis P. aeruginosa 1T-14 S. mutans ALAGLAGLISGK 23 S. aureus S. epidermidis C. xerosis 1T-15 S. mutans DVILRVEAQ 24 1T-16 P. aeruginosa IDMR 25 1T-17 S. mutans NNAIVYIS 26 1T-18 S. aureus YSKTLHFAD 27 S. epidermidis C. striatum P. aeruginosa 1T-19 S. aureus PGAFRNPQMPRG 28 S. epidermidis P. aeruginosa 1T-20 S. mutans PALVDLSNKEAVWAVLDDHS 29 P. aeruginosa 1T-21 S. mutans YVEEAVRAALKKEARISTEDTPVNLPSF 30 P. aeruginosa DC 1T-22 S. epidermidis VPLDDGTRRPEVARNRDKDRED 31 P. aeruginosa 1T-23 S. mutans PALVDLSNKEAVWAVLDDHS 32 P. aeruginosa 1T-24 P. aeruginosa EEAEEKLAEVSQAVKRLVR 33 1T-25 S. aureus VGLDVSVLVLFFGLQLLSVLLGAMIR 34 S. epidermidis C. xerosis C. striatum P. aeruginosa 1T-26 S. mutans LTILPTTFFAIIVPILAVAFIAYSGFKIKGI 35 S. aureus VEHKDQW S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-27 S. mutans ALFVSLEQFLVVVAKSVFALCHSGTLS 36 S. aureus S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-28 P. aeruginosa VSRDEAMEFIDREWTTLQPAGKSHA 37 1T-29 S. mutans GSVIKKRRKRMSKKKHRKMLRRTRVQ 38 S. aureus RRKLGK S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-30 S. aureus GKAKPYQVRQVLRAVDKLETRRKKGG 39 S. epidermidis R C. xerosis C. striatum P. aeruginosa 1T-31 S. mutans NATGTDIGEVTLTLGRFS 40 P. aeruginosa 1T-32 S. mutans VSFLAGWLCLGLAAWRLGNA 41 1T-33 S. aureus VRTLTILVIFIFNYLKSISYKLKQPFENNL 42 S. epidermidis AQSMISI C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-34 S. aureus AFWLNILLTLLGYIPGIVHAVYIIAKR 43 S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-35 P. aeruginosa EICLTLVFPIRGSYSEAAKFPVPIHIVEDG 44 TVELPK 1T-36 S. aureus VYRHLRFIDGKLVEIRLERK 45 S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-37 S. mutans YIVGALVILAVAGLIYSMLRKA 46 S. aereus S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-38 S. mutans VMFVLTRGRSPRPMIPAY 47 S. aereus S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-39 S. mutans FGFCVWMYQLLAGPPGPPA 48 P. aeruginosa 1T-40 S. mutans QRVSLWSEVEHEFR 49 P. aeruginosa 1T-41 S. mutans KRGSKIVIAIAVVLIVLAGVWVW 50 S. aureus S. epidermidis C. jeikeium C. striatum P. aeruginosa 1T-42 S. aureus TVLDWLSLALATGLFVYLLVALLRADR 51 S. epidermidis A C. xerosis C. striatum P. aeruginosa 1T-43 C. jeikium DRCLSVLSWSPPKVSPLI 52 P. aeruginosa 1T-44 S. mutans DPALADFAAGMRAQVRT 53 S. aureus S. epidermidis C. jeikeium C. striatum P. aeruginosa 1T-45 S. aureus WTKPSFTDLRLGFEVTLYFANR 54 S. epidermidis C. striatum P. aeruginosa 1T-46 S. aureus FSFKQRVMFRKEVERLR 55 S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-47 S. mutans VIKISVPGQVQMLIP 56 S. epidermidis P. aeruginosa 1T-48 S. aureus KLQVHHGRATHTLLLQPPLCAPGTIR 57 S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-49 S. aureus SLVRIHDQQPWVTRGAFIDAARTCS 58 S. epidermidis C. jeikeium P. aeruginosa 1T-50 P. aeruginosa HSDEPIPNILFKSDSVH 59 1T-51 S. aureus GKPKRMPAEFIDGYGQALLAGA 60 P. aeruginosa 1T-52 S. aureus DEYPAKLPLSDKGATEPRRH 61 C. xerosis P. aeruginosa 1T-53 P. aeruginosa SDILAEMFEKGELQTLVKDAAAKANA 62 1T-54 S. epidermidis RWVSCNPSWRIQ 63 C. xerosis C. striatum P. aeruginosa 1T-55 C. xerosis NHKTLKEWKAKWGPEAVESWATLLG 64 P. aeruginosa 1T-56 C. xerosis LALIGAGIWMIRKG 65 P. aeruginosa 1T-57 P. aeruginosa RLEYRRLETQVEENPESGRRPMRG 66 1T-58 P. aeruginosa CDDLHALERAGKLDALLSA 67 1T-59 S. aureus AVGNNLGKDNDSGHRGKKHRKHKHR 68 S. epidermidis P. aeruginosa 1T-60 S. aureus YLTSLGLDAAEQAQGLLTILKG 69 S. epidermidis C. jeikeium C. striatum P. aeruginosa 1T-61 P. aeruginosa HATLLPAVREAISRQLLPALVPRG 70 1T-62 S. epidermidis GCKGCAQRDPCAEPEPYFRLR 71 P. aeruginosa 1T-63 S. aureus EPLILKELVRNLFLFCYARALR 72 S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-64 S. aureus QTVHHIHMHVLGQRQMHWPPG 73 S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-65 S. mutans HARAAVGVAELPRGAAVEVELIAAVRP 74 S. aureus S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-66 S. mutans DTDCLSRAYAQRIDELDKQYAGIDKPL 75 S. aureus S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-67 S. aureus GQRQRLTCGRVSGCSEGPSREAAR 76 S. epidermidis C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-68 S. mutans GGTKEIVYQRG 77 S. aureus C. jeikeium C. xerosis C. striatum P. aeruginosa 1T-69 S. mutans ILSQEADRKKLF 78 P. aeruginosa 1T-70 S. aureus NRQAQGERAHGEQQG 79 C. jeikeium P. aeruginosa 1T-71 P. aeruginosa KIDTNQWPPNKEG 80 1T-72 P. aeruginosa EPTDGVACKER 81 1T-73 S. pneumoniae GWWEELLHETILSKFKITKALELPIQL 82 1T-74 S. pneumoniae DIDWGRKISCAAGVAYGAIDGCATTV 83 1T-75 S. pneumoniae GVARGLQLGIKTRTQWGAATGAA 84 1T-76 S. pneumoniae EMRLSKFFRDFILWRKK 85 1T-77 S. pneumoniae EMRISRIILDFLFLRKK 86 1T-78 S. pneumoniae FFKTIFVLILGALGVAAGLYIEKNYIDK 87 1T-79 S. pneumoniae FGTPWSITNFWKKNFNDRPDFDSDRRR 88 Y 1T-80 S. pneumoniae GGNLGPGFGVIIP 89 1T-81 S. pneumoniae AIATGLDIVDGKFDGYLWA 90 1T-82 S. pneumoniae FGVGVGIALFMAGYAIGKDLRKKFGKS 91 C 1T-83 S. pneumoniae QKPRKNETFIGYIQRYDIDGNGYQSLPC 92 PQN 1T-84 S. pneumoniae FRKKRYGLSILLWLNAFTNLVNSIHAFY 93 MTLF 1T-85 A. naeslundii VMASLTWRMRAASASLPTHSRTDA 94 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-86 S. mitis HRKNPVLGVGRRHRAHNVA 95 S. oralis S. salivarious 1T-87 S. mitis EAVGQDLVDAHHP 96 S. mutans S. oralis 1T-89 S. mitis HEDDKRRGMSVEVLGFEVVQHEE 97 S. mutans 1T-90 S. gordonii RNVIGQVL 98 S. mitis S. mutans S. oralis S. sanguinis 1T-91 S. mitis TSVRPGAAGAAVPAGAAGAAGAGWR 99 S. mutans WP S. oralis S. sanguinis 1T-92 S. mitis GQDEGQRRAGVGEGQGVDG 100 S. mutans 1T-93 S. epidermidis AMRSVNQA 101 S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-94 S. mitis DQVAHSGDMLVQARRRDS 102 S. mutans S. oralis 1T-95 S. gordonii GHLLRVGGRVGGVGGVAGACAQPFGG 103 S. mitis Q S. mutans S. oralis S. sanguinis 1T-96 S. gordonii VAGACAQPFGGQ 104 S. mitis S. mutans S. oralis S. sanguinis 1T-97 A. naeslundii GVAERNLDRITVAVAIIWTITIVGLGLV 105 F. nucleatum AKLG P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-98 A. naeslundii VRSAKAVKALTAAGYTGELVNVSGGM 106 F. nucleatum KAWLGQ P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-99 S. gordonii MKAWLGQ 107 S. mitis S. mutans S. oralis S. sanguinis 1T-100 S. gordonii LDPLEPRIAPPGDRSHQGAPACHRDPLR 108 S. mitis GRSARDAER S. mutans 1T-101 A. naeslundii RLRVGRATDLPLTSFAVGVVRNLPDAP 109 P. gingivalis AH S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-102 A. naeslundii WKRLWPARILAGHSRRRMRWMVVWR 110 F. nucleatum YFAAT P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-103 A. naeslundii AQFYEAIITGYALGAGQRIGQL 111 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-104 S. mitis RAVAAHLQGRHHGHQVRRQRHGQR 112 1T-105 S. epidermidis GEGLPPPVLHLPPPRMSGR 113 S. gordonii S. mitis S. mutans S. oralis 1T-106 S. gordonii DALRRSRSQGRRHR 114 S. mitis S. mutans S. oralis S. salivarious 1T-107 A. naeslundii SPVPRFTAVGGVSRGSP 115 S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-108 S. gordonii WGPLGPERPLW 116 S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-109 A. naeslundii VTTNVRQGAGS 117 S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-110 A. naeslundii LAAKTAVCVGRAFM 118 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-111 A. naeslundii GRLSRREEDPATSIILLRGAYRMAVF 119 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-112 S. gordonii SDNDGKLILGTSQ 120 1T-113 S. mitis HGAHQRTGQRLHHHRGRTVSGCRQNP 121 VAGVDPDEHR 1T-114 A. naeslundii RQAPGPGLVTITAACSAPGSRSR 122 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-115 A. naeslundii LLIERFSNHH 123 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-116 A. naeslundii MILHRRRDR 124 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-117 S. mutans GPGVVGPAPFSRLPAHALNL 125 1T-118 A. naeslundii TASPPAPSDQGLRTAFPATLLIALAALA 126 F. nucleatum RISR P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-119 S. gordonii SPATQKAPTRAQPSRAPVQDCGDGRPT 127 S. mitis AAPDDVERLSPR S. mutans S. oralis 1T-120 A. naeslundii DVRDRVDLAGADLCAAHATR 128 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-121 S. gordonii FAKETGFGIGGAQEGWWIIADIYGPNPF 129 S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-122 S. mitis GAIPDPVTHRVDWEEDHQTRPSR 130 1T-123 S. gordonii LVRRNAVAGRSDGLAGAEQLDLVRLQ 131 GVL 1T-124 S. mitis LFDERNKIA 132 S. mutans S. oralis 1T-125 S. epidermidis DAITGGNPPLSDTDGLRP 133 S. gordonii S. mutans S. oralis 1T-126 S. gordonii QGLARPVLRRIPL 134 S. mitis S. mutans 1T-127 A. naeslundii YDPVPKRKNKNSEGKREE 135 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-128 A. naeslundii SGSAIRMLEIATKMLKR 136 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-129 A. naeslundii YDKYIKYLSIQPPFIVYFI 137 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-130 A. naeslundii QKIIDMSKFLFSLILFIMIVVIYIGKSIGG 138 F. nucleatum YSAIVSSIMLELDTVLYNKKIFFIYK P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-131 A. naeslundii DEVWKMLGI 139 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-132 A. naeslundii YSKKLFEYFYFIIFILIRYLIFYKIIQNKNY 140 F. nucleatum YINNIAYN P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-133 A. naeslundii YFIKDDNEALSKDWEVIGNDLKGTIDK 141 P. gingivalis YGKEFKVR S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-134 A. naeslundii SRLVREIKKKCRKS 142 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-135 A. naeslundii FESLLPQATKKIVNNKGSKINKIF 143 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-136 A. naeslundii ELLTQIRLALLYSVNEW 144 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-137 A. naeslundii PLNFYRAVKENRLPLSEKNINDFTNIKL 145 F. nucleatum KVSPKLINLLQESSIFYNFSPKKRNTN P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-138 A. naeslundii YPNEYCIFLENLSLEELKEIKAINGETLN 146 F. nucleatum LEEIINERKNLKD P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-139 A. naeslundii AVAGAAVGALLGNDARSTAVGAAIGG 147 S. gordonii ALGAGAGELTKNK S. mitis S. mutans S. oralis 1T-140 A. naeslundii IKGTIAFVGEDYVEIRVDKGVKLTFRKS 148 F. nucleatum AIANVINNNQQ P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-141 F. nucleatum KKFIILLFILVQGLIFSATKTLSDIIAL 149 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-142 A. naeslundii FTQGIKRIVLKRLKED 150 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-143 A. naeslundii MPKRHYYKLEAKALQFGLPFAYSPIQL 151 F. nucleatum LK P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-144 A. naeslundii IIELHPKSWTQDWRCSFL 152 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-145 S. mitis VEAGKRNISLENIEKISKGLGISISELFKY 153 S. mutans IEEGEDKIG S. oralis 1T-146 A. naeslundii RNSADNQTKIDKIRIDISLWDEHLNIVK 154 F. nucleatum QGK P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-147 A. naeslundii GVENRRFYERDVSKVSMMTSEAVAPR 155 F. nucleatum GGSK P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-148 A. naeslundii IVELDDTTILERALSMLGEANA 156 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-149 A. naeslundii SVRAVKPIDETVARHFPGDFIVN 157 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-150 A. naeslundii YINRRLKKAFSDADIKEAPAEFYEELRR 158 F. nucleatum VQYV P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-151 A. naeslundii SVRAVKPIDEIVAWHFPGDFIVN 159 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-152 A. naeslundii YVSADESAYNHIVTDDIPLADRRIEAVQ 160 F. nucleatum Q P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-153 A. naeslundii YIACPGYFY 161 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-154 P. gingivalis YFSFLEIVGMARR 162 1T-155 A. naeslundii LKLAFGVYPFQAMSQSDTAVSERNVL 163 F. nucleatum WR P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-156 A. naeslundii GRFQISIRGEEKSKVKVQGKGTFTDRNT 164 F. nucleatum T P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-157 A. naeslundii RRFRKTTENREKSKNKKAVLGLSTTST 165 F. nucleatum ASY P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-158 A. naeslundii WENKPSPLGSIKKLQGLVYRLIGYRHF 166 F. nucleatum WV P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-159 P. gingivalis IFSLHHFALICSEMGTFAVSKRAKYKWE 167 VL 1T-160 A. naeslundii AQYKYINKLLN 168 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-161 A. naeslundii NKVLQVEVMWDGSVVGRPAGVISIKSS 169 F. nucleatum KKG P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-162 A. naeslundii QKAKEESDRKAAVSYNGFHRVNVVSIP 170 F. nucleatum K P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-163 A. naeslundii MENILIYIPMVLSPFGSGILLFLGKDRRY 171 F. nucleatum ML P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-164 A. naeslundii KKSHSQGKRKLKDLNSAYKIDNQLHYA 172 F. nucleatum LR P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-165 A. naeslundii CYDSFDFSIFVTFANRMKLSVGS 173 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-166 A. naeslundii AQSAGQIKRKSKVRIHV 174 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-167 A. naeslundii SRMSEHSPAGLVFEVGPMDKGSFIILDS 175 F. nucleatum YHPTVKK P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-168 A. naeslundii ELHRIMSTEKIGAVTKMNFDTAPIMSILP 176 F. nucleatum IDIYPKEVGIGS P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-169 A. naeslundii FARVRRLHQNRILTQPLTNLKYCLRQPI 177 F. nucleatum YSD P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-170 P. gingivalis AYGKVFSMDIMLSENDKLIVLRISHHSA 178 WH 1T-171 A. naeslundii SVRAVKPIDKTVARHFPGDFIVN 179 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-172 A. naeslundii FEGLKNLLGDDII 180 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-173 A. naeslundii LFRKEDQEHVLL 181 F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-174 A. naeslundii SGGSDTDGSSSGEPGSHSGDL 182 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-175 A. naeslundii GEPGSHSGDL 183 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-176 A. naeslundii PVGDIMSGFLRGANQPRFLLDHISFGS 184 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-177 P. gingivalis GTNVPTQILGYSREERFDYEPAPEQR 185 S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-178 A. naeslundii LLASHPERLSLGVFFVYRVLHLLLENT 186 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-179 A. naeslundii TCYPLIQRKTDRAYEA 187 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-180 A. naeslundii VVFGGGDRLV 188 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-181 A. naeslundii YGKESDP 189 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-182 A. naeslundii LTASICRQWNDNSTPYQR 190 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-183 A. naeslundii PLRSFVAEKAEHAFRVVRIADFDFGHS 191 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-184 A. naeslundii ALLVLNLLLMQFFFGKNM 192 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-185 A. naeslundii HYHFLLEFGFHKGDYLE 193 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-188 S. sanguinis HRKDVYKK 194 1T-190 A. naeslundii IQIIVNAFVEKDKTGAVIEVLYASNNHE 195 F. nucleatum KVKAKYEELVAIS P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-192 S. sanguinis ILVLLALQVELDSKFQY 196 1T-193 S. sanguinis LMIFDKHANLKYKYGNRSFGVEAIM 197 1T-195 S. mutans AASGFTYCASNGVWHPY 198 1T-196 F. nucleatum KPEKEKLDTNTLMKVVNKALSLFDRLL 199 S. sanguinis IKFGA 1T-197 A. naeslundii TEILNFLITVCADRENWKIKHGLSDSVL 200 F. nucleatum LIFFARFTGAEYW P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-198 P. gingivalis MPVSKKRYMLSSAYATALGICYGQVAT 201 S. epidermidis DEKESEITAIPDLLDYLSVEEYLL S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-199 S. sanguinis RAGRIKKLSQKEAEPFEN 202 1T-200 A. naeslundii MRFKRFDRDYALSGDNVFEVLTASCDV 203 F. nucleatum IERNLSYREMCGLMQ S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-201 S. sanguinis KRKHENVIVAEEMRVIKN 204 1T-202 A. naeslundii LCRLEKLCKQFLRQDKVVTYYLMLPYK 205 F. nucleatum RAIEAFYQELKERS P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-203 A. naeslundii YPFCLATVDHLPEGLSVTDYERVQRLV 206 F. nucleatum SQFLLNKEER P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-207 F. nucleatum SPLEKYGTGSMTALTFLLGCCLLVLSKK 207 S. sanguinis SR 1T-208 Unanalyzed KRKRWAILTLFLAGLGAVGIVLATF 208 1T-215 S. sanguinis VCFKDISVFLSPFRGQEVLFCGKAKHSL 209 IYVIGT 1T-216 S. sanguinis FFLNVIAIRIPHF 210 1T-217 F. nucleatum MLSNVLSRSVVSPNVDIPNSMVILSPLLI 211 S. sanguinis SISNYH 1T-218 F. nucleatum KLIFAALGLVFLLIGLRDSRSK 212 S. sanguinis 1T-219 S. sanguinis RNINVSATFITEKSLV 213 1T-221 A. naeslundii DIGRIIGKKGRTITAIRSIVYSVPTQGKK 214 F. nucleatum VRLVIDEK P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-222 F. nucleatum RIEASLISAIMFSMFNAIVKFLQK 215 S. sanguinis 1T-223 A. naeslundii NQKMEINSMTSEKEKMLAGHFHNEAN 216 F. nucleatum FAVIFKYSLFYNFF P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-225 A. naeslundii RRSLGNSASFAEWIEYIRYLHYIIRVQFI 217 F. nucleatum HFFSKNKKI P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-226 A. naeslundii KLQEKQIDRNFERVSGYSTYRAVQAAK 218 F. nucleatum AKEKGFISLEN S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-228 A. naeslundii IFKLFEEHLLYLLDAFYYSKIFRRLKQGL 219 F. nucleatum YRRKEQPYTQDLFRM P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-230 A. naeslundii EFLEKFKVLKQPRKANNISKNRVAMIFL 220 F. nucleatum TIHKSRGFLSSPY P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-233 A. naeslundii TDQELEHLIVTELESKRLDFTYSKDITEF 221 P. gingivalis FDEAFPEYDQNY S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-234 A. naeslundii DNFYLILKMEERGKSKKTSQTRGFRAFF 222 F. nucleatum DIIRKKIKKEDGK P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-237 S. sanguinis EDPVPNHFTLRRNKKEKPSKS 223 1T-238 A. naeslundii IFNRRKFFQYFGLSKEAMVEHIQPFILDI 224 F. nucleatum WQIHLF P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-239 A. naeslundii ADDLLNKRLTDLIMENAETVKTIDLDN 225 S. gordonii SD S. mitis S. mutans S. oralis S. sanguinis 1T-240 A. naeslundii VILGNGISNIAQTLGQLPNIAWVWIYMV 226 F. nucleatum LIAALLEESNVC P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-242 F. nucleatum KQVQNTTLIICGTVLLGILFKSYLKSQKS 227 S. sanguinis V 1T-243 A. naeslundii SENIARFAAAFENEQVVSYARWFRRSW 228 P. gingivalis RGSGSSSRF S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-248 S. sanguinis IGGALNSCG 229 1T-249 F. nucleatum VFSVLKHTTWPTRKQSWHDFISILEYSA 230 S. sanguinis FFALVIFIFDKLLTLGLAELLKRF 1T-250 S. mitis LVQGDTILIENHVGTPVKDDGKDCLIIR 231 S. mutans EADVLAVVND S. oralis 1T-252 F. nucleatum MKKNLKRFYALVLGFIIGCLFVSILIFIG 232 S. sanguinis Y 1T-253 A. naeslundii KTKESLTQQEKKFLKDYDRKSLHHFRD 233 F. nucleatum ILTYCFILDKLTNK P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-256 S. sanguinis KGKSLMPLLKQINQWGKLYL 234 1T-257 A. naeslundii IILAKAADLAEIERIISEDPFKINEIANYDI 235 F. nucleatum IEFCPTKSSKAFEKVLK P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-258 A. naeslundii TINIDDKVLDYLKKINSKAITIDLIGCAS 236 F. nucleatum P. gingivalis T. denticola S. mitis S. mutans S. oralis 1T-259 F. nucleatum EKLKKILLKLAVCGKAWYTL 237 P. gingivalis T. denticola S. mitis S. mutans S. oralis S. sanguinis 1T-260 A. naeslundii NILYFIHDENQWEPQKAEIFRGSIKHCA 238 P. gingivalis WLSS S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-261 F. nucleatum SFEKNKIENNLKIAQAYIYIKPKPRICQA 239 S. mutans S. oralis S. sanguinis 1T-262 A. naeslundii LSLPLIVLTKSI 240 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-263 A. naeslundii FIAVSFTGNPATFKLVIGCKADN 241 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. oralis S. salivarious S. sanguinis 1T-264 S. sanguinis LEGKFYMAEDFDKTPECFKDYV 242 1T-265 A. naeslundii GMFENLLMINFQIMNDLKIEIVVKDRIC 243 F. nucleatum AV P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-266 S. sanguinis RAGTWLVVDEIR 244 1T-267 A. naeslundii RIKEERKNRSYKFFIWRLFDEKTGFI 245 F. nucleatum P. gingivalis T. denticola S. mitis S. mutans S. oralis S. sanguinis 1T-268 F. nucleatum PITPKKEKCGLGTYAPKNPVFSKSRV 246 S. mutans S. oralis S. sanguinis 1T-269 F. nucleatum PLYVAAVEKINTAKKH 247 S. mutans S. oralis S. sanguinis 1T-270 F. nucleatum VHEFDIQKILQNR 248 S. mutans S. oralis S. sanguinis 1T-271 A. naeslundii FLIQKFLLIKTFPPYRKKYVVIVSQTGTA 249 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-272 F. nucleatum QLAPIDKQLKAVKKIAFYESESTAAKAV 250 S. mutans TVA S. oralis S. sanguinis 1T-273 F. nucleatum YNEPNYKWLESYKIYKQRCEDRTGMY 251 P. gingivalis YTEET T. denticola S. mitis S. mutans S. oralis 1T-274 F. nucleatum ETTTEINAIKLHRIKQRSPQGTRRVN 252 S. mutans S. oralis S. sanguinis 1T-275 A. naeslundii QVLKNFSISRRYKINNPFFKILLFIQLRTL 253 F. nucleatum P. gingivalis T. denticola S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-276 A. naeslundii ILTLLILGSIGFFILKIKLKLGRF 254 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-277 A. naeslundii IYYMRFVNKPLEKTFFKI 255 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-278 A. naeslundii SINSSAGIQPHCLSSSFVLRTKHCFY 256 F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-279 A. naeslundii FVLRTKHCFY 257 F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-280 A. naeslundii TNNKNKVIIKAIKFKNKDFINLDLFIYRR 258 F. nucleatum P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-281 A. naeslundii KYEKLTKENLFIRNSGNMCVFIYFLFFG 259 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-282 F. nucleatum ISLVFPAYT 260 P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-283 A. naeslundii LCTKLEDKQRGRIPAELFIISPIKILERND 261 F. nucleatum AL P. gingivalis T. denticola S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-284 A. naeslundii FQYYFSLKRV 262 F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-285 A. naeslundii FFPYYLADFYKQLKFLNEYQTKNKDKV 263 F. nucleatum VEFK P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-286 S. sanguinis LGFFNNKADLVKADTERDNRMSSLKIK 264 DL 1T-287 P. gingivalis KGYPLPFQYRLNNH 265 T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-288 F. nucleatum RWVGGEPSADIYLSAKDTKT 266 S. gordonii S. salivarious S. sanguinis 1T-289 F. nucleatum EPSADIYLSAKDTKT 267 P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. sanguinis 1T-290 A. naeslundii IINQLNLILLRLMEILIL 268 F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-291 A. naeslundii DMKIIKLYIKILSFLFIKYCNKKLNSVKL 269 F. nucleatum KA P. gingivalis T. denticola S. mitis S. mutans S. oralis 1T-292 A. naeslundii IINQLNLILLRLMEILIL 270 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-293 A. naeslundii HVEDCFLLSNARTTAIHGRANPARGEPR 271 F. nucleatum TRSE P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-294 T. denticola YDKIADGVFKIGKRGVL 272 1T-295 S. mitis KYKLKKIIL 273 S. salivarious S. sanguinis 1T-296 A. naeslundii EYSQQSFKAKPCSERGVLSP 274 F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-297 A. naeslundii RSLRLNNALTKLPKLWYNRIKEAFYAY 275 F. nucleatum NDYDK T. denticola S. mitis S. mutans S. oralis 1T-298 A. naeslundii ILNKKPKLPLWKLGKNYFRRFYVLPTFL 276 F. nucleatum A P. gingivalis T. denticola S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-299 A. naeslundii SMLTSFLRSKNTRSLKMYKDVHF 277 F. nucleatum S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-300 A. naeslundii PLIISKAQIKMSGDILGSCFKLFYLRPFF 278 F. nucleatum P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-301 F. nucleatum SKLPRVLDASLKL 279 S. gordonii S. sanguinis 1T-302 A. naeslundii IIIILPKIYLVCKTV 280 P. gingivalis S. epidermidis S. gordonii S. mitis S. mutans S. oralis S. salivarious S. sanguinis 1T-303 A. naeslundii LDYENMDCKKRIRI 281 F. nucleatum P. gingivalis S. gordonii S. mitis S. mutans S. oxalis S. salivarious S. sanguinis 1T-304 P. gingivalis STAGEASRRTASEASRRTAAKLRG 282 TT-305 F. nucleatum ARNALNMRDVPVDAAIIGIIDGMDEE 283 TT-306 F. nucleatum KILNEAEGKLLKVIEKNGEIDIEEI 284 TT-307 F. nucleatum NGDKKAKEELDKWDEVIKELNIQF 285 TT-308 F. nucleatum GLVIIPNLIALIILFSQVRQQTKDYFSNPK 286 LSSR TT-309 F. nucleatum EPLPLTKYDKKDTEMKKVFKEILAGKV 287 GYEKEEE TT-310 F. nucleatum TKLKKNNKLLSAKKENTLHTKDK 288 TT-311 S. mutans AIFDAMHNL 289 S. sobrinus PVCFBP2461 P. fluorescens DLys-Dorn-Gly-DThr-Thr-Gln-Gly-DSer- 290 cDOrn CHA0 P. fluorescens Asp-DOrn-Lys-c(Thr-Ala-Ala-DOrn-Lys) 291 CFBP2461 P. putida Asp-Lys-DAsp-Ser-DThr-DAla-Thr-DLys- 292 cOrn NCPPB2192 P. tolaasii DSer-Lys-Ser-DSer-Thr-DSer-Orn-Thr- 293 DSer-cDOrn PyC-E P. aeruginosa DSer-Arg-DSer-Orn-c(Lys-Orn-Thr-Thr) 294 PyR P. aeruginosa DSer-Dab-Orn-DGln-Gln-DOrn-Gly 295 PyPaTII P. aeruginosa DSer-DOrn-Orn-Gly-DThr-Ser-cOrn 296 Py Pap P. aptata DAla-Lys-Thr-DSer-Orm-cOrn 297 Py Pau P. aureofaciens DSer-DOrn-Gly-DThr-Thr-Gln-Gly-DSer- 298 cDOrn Ps P. fluorescens Lys-DAsp-Ala-DThr-Ala-cDOrn 299 Py I-III P. fluorescens Asn-DOrn-Lys-c(Thr-DAla-DAla-DOrn- 300 Lys) Py Gm P. fluorescens DAla-Lys-Gly-Gly-Asp-DGln-DSer-Ala- 301 DAla-DAla-Ala-cOrn Py Pf 12 P. fluorescens DSer-Lys-Gly-Orn-DSer-Ser-Gly-c(Lys- 302 DOrn-Glu-Ser) Py Pf P. fluorescens c(DSer-Dab)-Gly-Ser-Asp-Ala-Gly-DAla- 303 2798 Gly-cOrn Py Pf P. fluorescens Ser-Lys-Gly-Orn-c(Lys-DOrn-Ser) 304 13525 Py Pf P. fluorescens DAla-DLys-Gly-Gly-Asp-DGln-Dab-Ser- 305 17400 DAla-cOrn Py 51W P. fluorescens DAla-DLys-Gly-Gly-DAsp-DGln-DSer-Ala- 306 Gly-DThr-cOrn Py 9AW P. fluorescens DSer-Lys-His-DThr-Ser-cOrn 307 Ps A225 P. fluorescens DSer-DAla-DOrn-Gly-c(DSer-DAsp-DSer- 308 DThr) Py Pf 1.3 P. fluorescens DAla-DLys-Gly-Gly-Asp-c(DGln-Dab)-Gly- 309 Ser-cOrn Py Pf P. fluorescens DSer-Lys-Gly-Orn-Ser-DSer-Gly-c(Lys- 310 18.1 DOrn-Ser) Py Pf P. fluorescens DSer-DOrn-Ala-Gly-DThr-Ala-cOrn 311 PL7 Py Pf P. fluorescens DLys-DOrn-Ala-Gly-DThr-Ser-cOrn 312 PL8 Py Pf P. fluorescens DSer-DSer-Orn-DSer-DSer-c(DSer-Orn- 313 BTP7 Lys-Lys) Ps 589A P. putida Asp-Lys-Asp-DSer-Thr-DAla-DGlu-DSer- 314 cOrn Py Pp 1, 2 P. putida Ser-Thr-DSer-Orn-Asp-DGln-Dab-Ser- 315 DThr-cOrn Py Pp P. putida Asp-DOrn-DDab-Thr-Gly-DSer-Ser-Asp- 316 C2, 3 Thr Py G4R P. putida Asp-Orn-DAsp-Dab-Gly-Ser-cOrn 317 Py P. putida Asp-DOrn-DDab-Thr-Gly-DSer-DSer-Thr- 318 PpBTP16 Asp Py P. putida DSer-DAla-DOrn-Gly-DAla-DAsp-c(DSer- 319 Pp39167 DThr) iPy Pp P. putida Asp-Ala-Asp-DOrn-Ser-cOrn 320 BTP1 Py P. tolaasii DSer-Lys-Ser-DSer-Thr-DSer-Orn-Thr- 321 PT2192 DSer-Orn Ps 7SR1 Pseudomonas spp. DSer-DAsp-DThr-c(DSer-D-Orn-Ala-Gly- 322 DSer) Ps A214 Pseudomonas spp. DSer-DAla-Gly-DSer-DAla-DAsp-DThr- 323 DOrn Azoverdin Pseudomonas spp. Hse-DHse-Dab-DOrn-DSer-Orn 324 A. macrocytogenes PF-S024 Corynebacteria SKRGRKRKDRRKKKANHGKRPNS 325 spp. PF-001 S. epidermidis MNNWIIVAQLSVTVINEIIDIMKEKQKG 326 M. luteus GK P. mirabilis E. coli P. aeruginosa C. albicans MRSA E. faecalis C. jeikeium PF-002 S. epidermidis NDDAQ 327 P. mirabilis C. albicans C. jeikeium C. jejuni PF-003 S. epidermidis MNNWIKVAQISVTVINEVIDIMKEKQN 328 M. luteus GGK P. mirabilis C. albicans MRSA C. jeikeium PF-004 S. epidermidis ARLSKAIIIAVIVVYHLDVRGLF 329 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium PF-005 S. epidermidis MESIFKIKLMNGICRSENMNMKKKNKG 330 E. coli EKI MRSA S. pneumoniae E. faecalis PF-006 S. epidermidis MGIIAGIIKFIKGLIEKFTGK 331 M. luteus E. coli P. aeruginosa MRSA E. faecalis C. jeikeium C. jejuni PF-007 S. epidermidis MGIIAGIIKVIKSLIEQFTGK 332 M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-008 S. epidermidis MIEIGSIAYLNGGSKKYNHILNQENR 333 M. luteus MRSA C. jejuni PF-009 M. luteus SKKYNHILNQENR 334 P. mirabilis C. albicans PF-010 S. epidermidis MDIDVNKLLQAFVYFKSFEKLRHNNS 335 M. luteus E. coli C. albicans PF-011 M. luteus MFCYYKQHKGDNFSIEEVKNIIADNEM 336 E. coli KVN P. aeruginosa S. pneumoniae C. jeikeium PF-012 S. epidermidis WRGPNTEAGGKSANNIVQVGGAPT 337 M. luteus P. mirabilis E. coli P. aeruginosa MRSA S. pneumoniae C. jeikeium C. jejuni PF-013 M. luteus LIQKGLNQTFIVVIRLNNFIKKS 338 P. mirabilis E. coli P. aeruginosa MRSA S. pneumoniae C. jeikeium C. jejuni PF-014 E. coli HPTDNKHN 339 C. jeikeium PF-015 E. faecalis SIDKRNLYNLKYYE 340 C. jeikeium PF-016 S. epidermidis RKQYDDLSFNFLY 341 E. faecalis C. jeikeium PF-017 E. coli ESIIE 342 PF-018 E. coli YYKTYFKEV 343 C. jeikeium PF-020 S. epidermidis MKIILLLFLIFGFIVVVTLKSEHQLTLFSI 344 M. luteus C. albicans MRSA S. pneumoniae E. faecalis PF-021 S. epidermidis FSLNFSKQKYVTVN 345 M. luteus P. mirabilis E. coli C. albicans E. faecalis C. jeikeium PF-022 M. luteus MINELKNKNSGIMNNYVVTKESKL 346 P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-023 M. luteus MTKNTIISLENEKTQINDSENESSDLRKA 347 C. jeikeium K PF-024 M. luteus DLRKAK 348 C. albicans MRSA E. faecalis C. jeikeium PF-025 S. epidermidis LLIIFRLWLELKWKNKK 349 M. luteus P. mirabilis E. coli P. aeruginosa MRSA E. faecalis C. jejuni PF-026 S. epidermidis SIHFIN 350 M. luteus P. mirabilis C. albicans MRSA E. faecalis C. jeikeium PF-027 M. luteus HNARKYLEFISQKIDGDKLTKEDSL 351 MRSA E. faecalis C. jejuni PF-028 S. epidermidis ALDCSEQSVILWYETILDKIVGVIK 352 M. luteus MRSA PF-029 S. epidermidis NSTNE 353 M. luteus C. albicans C. jejuni PF-030 S. epidermidis MTCHQAPTTTHQSNMA 354 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-031 M. luteus MPHHSTTSSRIVVPAHQSNMASTPNLSI 355 C. albicans TP PF-033 S. epidermidis MFIFKTTSKSHFHNNVKSLECIKIPINKN 356 M. luteus R E. coli P. aeruginosa C. albicans MRSA S. pneumoniae PF-034 M. luteus EPKKKHFPKMESASSEP 357 PF-035 S. epidermidis SFYESY 358 M. luteus E. coli C. albicans MRSA C. jeikeium C. jejuni PF-036 S. epidermidis ILNRLSRIVSNEVTSLIYSLK 359 M. luteus P. mirabilis E. coli C. albicans MRSA S. pneumoniae C. jejuni PF-037 S. epidermidis MTKKRRYDTTEFGLAHSMTAKITLHQA 360 M. luteus LYK P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-038 M. luteus MAYKDEGKETKFAVKGYKD 361 PF-039 P. mirabilis MLEEKNKSL 362 C. jeikeium PF-040 S. epidermidis MIHLTKQNTMEALHFIKQFYDMFFILNF 363 M. luteus NV P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-041 MRSA ELLVILPGFI 364 PF-042 S. epidermidis LLLSYFRYTGALLQSLF 365 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-043 M. luteus MIKNETAYQMNELLVIRSAYAK 366 C. jejuni PF-044 S. epidermidis KLKKYIHKPD 367 M. luteus MRSA C. jeikeium PF-045 S. epidermidis LDINDYRSTY 368 E. coli E. faecalis C. jejuni PF-046 E. coli LDFYLTKHLTLML 369 E. faecalis C. jeikeium PF-047 S. mutans NQEPSLQQDKEQKDNKG 370 PF-048 S. epidermidis LYFAFKKYQERVNQAPNIEY 371 M. luteus E. coli MRSA C. jeikeium C. jejuni PF-049 S. epidermidis AYYLKRREEKGK 372 MRSA C. jeikeium C. jejuni PF-050 S. epidermidis SYYLKRREEKGK 373 M. luteus E. coli C. jeikeium PF-051 S. epidermidis RFFNFEIKKSTKVDYVFAHVDLSDV 374 M. luteus P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-052 S. epidermidis QELINEAVNLLVKSK 375 M. luteus E. coli MRSA E. faecalis C. jeikeium C. jejuni PF-053 S. epidermidis KLFGQWGPELGSIYILPALIGSIILIAIVTL 376 M. luteus ILRAMRK E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-054 S. epidermidis VSISRFIGGGHVFNGNNKRNL 377 E. coli PF-055 S. mutans GHVFNGNNKRNL 378 PF-056 S. epidermidis AEQLFGKQKQRGVDLFLNRLTIILSILFF 379 M. luteus VLMICISYLGM P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-057 S. epidermidis TMIVISIPRFEEYMKARHKKWM 380 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-058 S. epidermidis FADQSQDNA 381 M. luteus E. coli C. albicans MRSA C. jeikeium C. jejuni PF-060 E. coli HSSHL 382 C. albicans C. jeikeium PF-061 S. epidermidis GYNSYKAVQDVKTHSEEQRVTAKK 383 S. pneumoniae PF-062 S. epidermidis MKKKRINNDILGRMIYSSSIDKRNLYNL 384 M. luteus KYYE E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium PF-063 S. epidermidis IAAIIVLVLFQKGLLQIFNWILIQLQ 385 M. luteus E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-064 E. coli DYYGKE 386 PF-065 M. luteus LEKNTRDNYFIHAIDRIYINTSKGLFPES 387 E. coli ELVAWG P. aeruginosa C. albicans MRSA S. pneumoniae C. jeikeium C. jejuni PF-066 M. luteus IKGTVKAVDETTVVITVNGHGTELTFEK 388 E. coli PAIKQVDPS C. jeikeium PF-067 S. epidermidis DLIVKVHICFVVKTASGYCYLNKREAQ 389 M. luteus AAI P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-068 S. epidermidis SHLINNFGLSVINPSTPICLNFSPVFNLLT 390 M. luteus VYGITCN P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-069 E. faecalis FDPVPLKKDKSASKHSHKHNH 391 C. jejuni PF-070 S. epidermidis SMVKSEIVDLLNGEDNDD 392 C. jejuni PF-071 S. epidermidis HCVIGNVVDIANLLKRRAVYRDIADVIK 393 E. coli MR P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-073 S. epidermidis CPSVTMDACALLQKFDFCNNISHFRHFF 394 M. luteus AIKQPIER P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-074 S. epidermidis RDIHPIYFMTKD 395 M. luteus MRSA PF-075 M. luteus FVNSLIMKDLSDNDMRFKYEYYNREKD 396 E. coli T P. aeruginosa MRSA C. jeikeium PF-076 S. epidermidis LYQYELLSKEEYLKCTLIINQRRNEQK 397 M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-097 C. jeikeium QPTQGEQGTRPRRPTPMRGLLI 398 PF-099 S. epidermidis EIIAYLEGRFANA 399 M. luteus E. coli C. jeikeium PF-101 S. mutans DPVPERQEQACACHRTAKPGK 400 PF-104 MRSA ERTAVNDLWI 401 C. jeikeium PF-123 M. luteus TTRPQVAEDRQLDDALKETFPASDPISP 402 E. coli PF-124 S. epidermidis MADGQIAAIAKLHGVPVATRNIRHFQSF 403 M. luteus GVELINPWSG P. mirabilis E. coli P. aeruginosa C. albicans MRSA E. faecalis C. jejuni PF-125 S. epidermidis YVVGALVILAVAGLIYSMLRKA 404 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jejuni PF-126 S. epidermidis FSPEAFGIGAAGVLGSFVTGLLIGWVAS 405 M. luteus LLRKAK P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-127 S. epidermidis MLRYLSLFAVGLATGYAWGWIDGLAA 406 M. luteus SLAV E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-128 M. luteus GIKVVAARFEEIQFSENFDSIILA 407 P. aeruginosa E. faecalis PF-129 S. epidermidis MKLLARDPWVCAWNDIW 408 MRSA E. faecalis C. jeikeium C. jejuni PF-130 E. faecalis LQRSDEESMPRRHEKYS 409 C. jeikeium C. jejuni PF-131 S. epidermidis RRAAARTKGNRR 410 E. coli MRSA C. jeikeium PF-132 S. epidermidis RPGDGAAEQGRSR 411 C. jeikeium PF-133 S. epidermidis GDPTAGQKPVECP 412 C. jeikeium C. jejuni M. smegmatis PF-134 S. epidermidis GKAMKRQDCSAL 413 C. jeikeium PF-135 S. epidermidis PPARPARIPQTPTLHGASLFRQRS 414 M. luteus E. coli P. aeruginosa MRSA C. jeikeium M. smegmatis PF-136 S. epidermidis LRGRVGRITACGYPP 415 M. luteus P. mirabilis E. coli MRSA E. faecalis C. jeikeium C. jejuni M. smegmatis PF-137 S. epidermidis VLGKGHDLLDVGKTALKSRVFAWLGG 416 P. mirabilis S S. pneumoniae C. jeikeium C. jejuni PF-138 S. epidermidis AVHHSLLFR 417 M. luteus P. mirabilis E. coli C. albicans MRSA C. jeikeium C. jejuni PF-139 S. epidermidis ALSKPAIQARTLCRRQDPP 418 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-140 S. epidermidis FHRRVIRASEWALTTRSFSTPLRSAAR 419 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-141 S. epidermidis VVRRFQGM 420 M. luteus C. albicans MRSA C. jeikeium PF-142 S. mutans GIDRGCQAAR 421 PF-143 S. epidermidis LSPRPIIVSRRSRADNNNDWSR 422 MRSA C. jeikeium PF-144 S. epidermidis RSGQPVGRPSRRAWLR 423 M. luteus E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-145 S. epidermidis GIVLTGRAGLVSGACSMALGVGLG 424 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-146 S. epidermidis GCGKRRIITKSASRDTR 425 M. luteus P. aeruginosa C. albicans MRSA C. jeikeium PF-147 S. epidermidis RRPRRRRSGHGQSASAA 426 M. luteus MRSA PF-148 S. epidermidis RRGCTERLRRMARRNAWDLYAEHFY 427 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-149 S. epidermidis GKVSVLTRVPRSLGGAPANQ 428 M. luteus E. coli MRSA C. jeikeium PF-150 S. epidermidis EIQAKGTG 429 MRSA PF-151 S. epidermidis EEYPARVPLSGEDVTEARRH 430 MRSA E. faecalis C. jeikeium PF-152 S. epidermidis VGYFIWKDSHSRKG 431 C. albicans MRSA E. faecalis C. jeikeium PF-153 M. luteus GILARADCSQIA 432 P. mirabilis E. coli MRSA PF-154 S. mutans GIKKSKHPSTDDYVVKTTIDSL 433 PF-155 C. jeikeium GRYGDDSKERQGRAQ 434 PF-156 S. epidermidis LITAEQPATAPIAGK 435 C. jeikeium PF-157 S. epidermidis HTAVVWLAGVSGCVALSHCEPA 436 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-158 S. epidermidis VRLESRPADLPE 437 PF-159 S. epidermidis TMAFVEKAQLRVPVGDDLPV 438 PF-160 S. epidermidis SFHASLTKNEKPIKSTG 439 PF-161 S. epidermidis RGRALASTATTRPARRRR 440 M. luteus E. coli C. jejuni PF-162 S. epidermidis GIRRLHSVENLNREISHRMAGLR 441 MRSA PF-163 S. epidermidis TSWLRAAERQEIGEPTKTFGEKTTSL 442 PF-164 S. epidermidis EEVSRALAGIGLGLGCRIG 443 M. luteus E. coli C. jeikeium PF-165 MRSA GPVSVVASLRRGTTVQRHSQNNHNKG 444 C. jejuni KP PF-166 E. coli SKAVSRKRSI 445 C. jeikeium PF-167 S. epidermidis AIEGVIKKGACFKLLRHEMF 446 E. coli C. albicans MRSA C. jeikeium C. jejuni PF-168 S. epidermidis VLPFPAIPLSRRRACVAAPRPRSRQRAS 447 M. luteus E. coli C. albicans MRSA C. jeikeium C. jejuni PF-169 S. epidermidis APGSAADSPRSRADD 448 E. coli C. albicans E. faecalis C. jeikeium PF-170 S. epidermidis RLARGRPTNLCGRRG 449 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jejuni PF-171 S. epidermidis TQVTLCRTW 450 E. coli P. aeruginosa S. pneumoniae PF-172 S. epidermidis LTGVRRPWRAPWAGTSGWALR 451 M. luteus E. coli P. aeruginosa MRSA E. faecalis C. jejuni PF-173 S. epidermidis AGRTAIVQGGG 452 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans C. jeikeium C. jejuni PF-174 S. epidermidis RGGDSPARRRPGLAGPGGPG 453 P. aeruginosa C. jeikeium PF-175 S. epidermidis RRRPAGQRPEKASQAMIAA 454 E. faecalis PF-176 S. epidermidis RLTSNQFLTRITPFVFAQH 455 M. luteus P. mirabilis E. coli C. albicans MRSA E. faecalis C. jeikeium PF-177 M. luteus VTSEPGIAHDIRLLPRAAAFR 456 MRSA E. faecalis C. jeikeium PF-178 S. epidermidis EVYSSPTNNVAITVQNN 457 M. luteus B. subtilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-180 S. epidermidis SGLGDLGFSSEAK 458 M. luteus P. aeruginosa C. albicans MRSA E. faecalis C. jejuni M. smegmatis PF-181 S. epidermidis GIAPRRNEWGAVGGR 459 M. luteus E. coli MRSA E. faecalis C. jeikeium PF-182 S. epidermidis LPATRDKTRVPASVAGAP 460 M. luteus E. coli E. faecalis C. jeikeium PF-183 S. epidermidis KPGISVENRQ 461 M. luteus E. coli C. albicans MRSA E. faecalis C. jeikeium PF-184 S. epidermidis LIADRHIRA 462 M. luteus E. coli P. aeruginosa C. albicans MRSA C. jeikeium PF-185 E. coli RPAQARQGPGGLIADRHIRA 463 P. aeruginosa PF-186 S. epidermidis DADKNLSLERDRFAWRVAAP 464 M. luteus E. coli P. aeruginosa MRSA C. jeikeium PF-187 S. epidermidis EIQKIAKGVSGQVYGPSRQITISKKR 465 M. luteus E. coli MRSA PF-188 S. epidermidis ARTFAGRLGTRYFGGLMRSTKA 466 M. luteus E. coli C. albicans MRSA E. faecalis PF-189 S. epidermidis GNLTRSREAARATQ 467 M. luteus C. albicans MRSA E. faecalis C. jejuni PF-190 S. epidermidis HFILRKPLLFMIHSLKTGPLDRF 468 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-191 E. coli QFCNFAWLFLASNNAQVSALA 469 P. aeruginosa C. jejuni PF-192 S. epidermidis VEEDEAPPPHY 470 M. luteus P. aeruginosa C. albicans E. faecalis C. jeikeium PF-193 S. epidermidis PPHCPPGHAKKGWC 471 M. luteus E. coli MRSA E. faecalis C. jejuni PF-194 C. jeikeium MKGNKLATAHEQPVKNSAPPL 472 PF-195 S. epidermidis EMAEGSADDRLRKTPRDC 473 M. luteus E. faecalis C. jeikeium PF-196 S. epidermidis TTARYIRRQCHTSITPLSQG 474 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jejuni PF-197 S. epidermidis CNALLRRGHPPSAL 475 M. luteus C. albicans E. faecalis C. jejuni PF-200 S. epidermidis GIELKSLIMAQIERWRQA 476 M. luteus MRSA E. faecalis C. jeikeium PF-201 S. epidermidis GCRPASLSDADPDGR 477 M. luteus E. coli C. albicans E. faecalis C. jeikeium C. jejuni PF-202 S. epidermidis ALNRASLRLALGE 478 M. luteus E. coli MRSA E. faecalis C. jeikeium C. jejuni PF-203 S. epidermidis SWKCHHLAI 479 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jejuni PF-204 S. epidermidis ALQKQDMNLPSVKNQLVFLKSTG 480 P. mirabilis E. coli P. aeruginosa C. albicans C. jejuni PF-205 S. epidermidis AGVLETPRCRGEYGAN 481 M. luteus E. coli P. aeruginosa C. albicans MRSA E. faecalis C. jeikeium C. jejuni PF-206 M. luteus KLRSASKKSLQEKSCGIMPEKPAG 482 C. albicans C. jeikeium C. jejuni PF-207 M. luteus AAGCRDLGSLSSLVTNPS 483 C. jeikeium PF-208 S. epidermidis DAYHCHLVRSPDAHDLSMRIGFV 484 C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-209 C. albicans NYAVVSHT 485 C. jeikeium C. jejuni PF-210 S. epidermidis EREDGCDAMPLP 486 P. aeruginosa C. albicans MRSA E. faecalis C. jeikeium C. jejuni PF-211 S. epidermidis DSFDSLSPFRERGGEREDGCDAMPLP 487 M. luteus E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-212 M. luteus NDSKASN 488 P. aeruginosa PF-213 S. epidermidis MTTGVDFIIEKV 489 PF-214 S. mutans GHLRVCWVFSASLLTPFRSATLI 490 S. epidermidis M. luteus E. coli P. aeruginosa A. baumannii PF-215 S. epidermidis ELKITNYNVNTVLYRYYKWGNDLCE 491 M. luteus P. aeruginosa A. baumannii PF-216 S. mutans ESVDKITEALEEDGFPAKVQ 492 E. coli PF-217 S. mutans DWEFTHKTIPQKK 493 PF-218 S. epidermidis SETPEKPVGTFFYSIYYKIIL 494 M. luteus P. aeruginosa A. baumannii PF-219 S. epidermidis FLALAVIAGLFKVILIYAAPYLK 495 M. luteus P. aeruginosa A. baumannii PF-221 S. epidermidis VFDNIDINF 496 M. luteus P. aeruginosa PF-222 S. epidermidis HIKETR 497 PF-223 S. epidermidis VKFCIECQTKLERKRR 498 M. luteus A. baumannii PF-224 S. epidermidis DYFYITLSQKNTF 499 P. aeruginosa A. baumannii PF-225 S. epidermidis MNCASPEFKKLMELYK 500 PF-226 A. baumannii LMFFSENMDKRDTLSGKFRYFAGSKVI 501 KLMNWLSENGK PF-228 S. mutans NQLGSQAFAQL 502 PF-229 S. epidermidis DPILIQIGFTRFALRKAEAEKIEIQVEEGV 503 M. luteus PA P. aeruginosa A. baumannii PF-230 S. mutans EDKPTNTIQEIKPVKWQ 504 PF-231 S. mutans AVRDFKKSVREEDEAASLNSPRTIDAQ 505 VKTSESTSVKS PF-232 S. epidermidis FDQLYALEREGKLDELLA 506 M. luteus PF-233 S. epidermidis DANAMARTTIAIVYILALIALTISYSL 507 M. luteus P. aeruginosa A. baumannii PF-234 S. epidermidis RTPYILRS 508 M. luteus PF-235 S. epidermidis GIPFSKPHKRQVNYMKSDVLAYIEQNK 509 M. luteus MAHTA PF-236 S. mutans KEIRTATVAELNAKRRLTSAEQALAEVS 510 S. epidermidis E. coli C. albicans S. pneumoniae E. faecalis PF-237 S. epidermidis YVKPKVGVHE 511 PF-238 S. mutans RNAVVVTEATFPKYEEEITNYLNRRFGE 512 S. epidermidis DWSLKLEKCSVA E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-239 S. mutans PKHNVVTGVSVDLDYKP 513 E. coli PF-240 S. mutans RITEVPPDEHSDR 514 E. coli PF-242 S. mutans KLFEDPLIKSKAVENFQTTWHEQCLAK 515 E. coli ELAKNM PF-244 S. epidermidis HMRTISYLLAFAKFSLFIPPKQSLKRL 516 M. luteus P. aeruginosa A. baumannii PF-245 S. epidermidis MNDVKPVVQPKQTLKAFLVQLLSVRA 517 M. luteus GVYIKQNNQLPKTKG P. aeruginosa A. baumannii PF-246 S. mutans QPDEKAEFFDPSLDKVYRHPTFYHIPDG 518 IEHM PF-247 S. epidermidis ETAASETH 519 PF-248 S. mutans ILSKLWFWMINSLGVVLLVSYWLLAK 520 S. epidermidis WGVA M. luteus E. coli P. aeruginosa A. baumannii PF-249 S. epidermidis INSRYKISF 521 M. luteus PF-252 S. mutans MKKLVAALAVIVILTGCVYDPVNYDKI 522 HDQEFQDHLRQNG PF-253 S. epidermidis VRDDDS 523 M. luteus PF-254 S. epidermidis FIYGVGFVPHFWLWKWLFSPWIAWPL 524 M. luteus MLLGYYIWFLT P. aeruginosa A. baumannii PF-255 P. aeruginosa DHKINESQHNPFRSDSNKQNVDFF 525 PF-256 S. epidermidis EYFKQVYVKNEKIYSFWICKDLSPKEA 526 AKRAEDILVKLK PF-257 S. epidermidis VWENRKKYLENEIERHNVFLKLGQEVI 527 KGLNALASRGR PF-259 S. epidermidis LPFSKIGRRVSYKKKDVLKYEQSKTVL 528 P. aeruginosa NTAQLATV A. baumannii PF-262 S. mutans DPHSEIDVTRYCQLHHFTCQTMQISERE 529 S. epidermidis FHYLIETQ M. luteus E. coli P. aeruginosa A. baumannii PF-263 S. epidermidis NLKKCPC 530 M. luteus A. baumannii PF-265 S. epidermidis MKTLFFPLFLIIFVLIIQALDQSYQKKIGI 531 M. luteus SKPQKHPEFMQ A. baumannii PF-266 S. mutans DQEKKNKTEESTEQ 532 PF-267 M. luteus SDDKRTD 533 PF-268 S. mutans EVLLSDLRPDIFSET 534 PF-270 S. epidermidis MYLTPYAWIAVGSIFAFSVTTIKIGDQN 535 M. luteus DEKQKSHKNDVHKR P. aeruginosa PF-271 S. epidermidis AAQPQTTSP 536 M. luteus P. aeruginosa A. baumannii PF-273 S. epidermidis LVGALLIFVALIYMVLKGNADKN 537 M. luteus P. aeruginosa A. baumannii PF-275 S. mutans LVSGVANTVKNTAHTVGNTAKHAGHV 538 AADTTVKATKKQQVK PF-276 S. epidermidis LDLALSTNSLNLEGFSF 539 PF-278 M. luteus LSLATFAKIFMTRSNWSLKRFNRL 540 A. baumannii PF-279 S. mutans SHIGFISISACLAVLLGIARLFVWTWVKF 541 S. epidermidis FA M. luteus E. coli P. aeruginosa A. baumannii PF-281 S. mutans SYNTYYNKLIHGQRTPDGM 542 E. coli PF-282 S. mutans QNNDTSAWCGSAHKNGNS 543 PF-283 B. subtilis MIRIRSPTKKKLNRNSISDWKSNTSGRF 544 B. fragilis FY C. difficile PF-284 C. difficile MRYITYSLIPRLLSKKVIHQQ 545 PF-285 S. mutans VPAKLLRVIDEIPE 546 PF-288 S. mutans IYQLLNIEYSEDD 547 E. coli PF-289 C. difficile MGRHLWNPSYFVATVSENTEEQIRKYR 548 KNK PF-291 S. mutans DVDGAIESEL 549 E. coli PF-292 S. epidermidis SFVSTTVRLIFEESKRYKF 550 B. subtilis B. fragilis PF-294 S. epidermidis DFLVNFLWFKGELNWGKKRYK 551 C. difficile PF-295 C. difficile NIQVYESECGNYIFKKSDESFLIDIFDKN 552 GTH PF-297 S. epidermidis ISKGIDDIVYVINKILSIGNIFKIIKRK 553 B. subtilis B. fragilis PF-299 B. subtilis LATKLKYEKEHKKM 554 PF-300 B. subtilis VKDVLLELFNKIIGA 555 C. difficile PF-301 C. difficile GIVLIGLKLIPLLANVLN 556 PF-304 S. mutans LVKDTSDIKNDLNNIEIVTSKNSNDIAKL 557 KSVK PF-305 C. difficile MREWICPSCNETHDRDINASINILKEGL 558 RLITIQNK PF-306 C. difficile GCILPHKKDNYNYIMSKFQDLVKITSKK 559 PF-307 S. epidermidis MKRRRCNWCGKLFYLEEKSKEAYCCK 560 B. subtilis ECRKKAKKVKK B. fragilis C. difficile PF-308 C. difficile QQYLILDRM 561 PF-309 S. mutans GIPGMTAAPAEENEQEENADEE 562 E. coli PF-311 C. difficile IDAVTKKKTTCMIRAPTKIPIAHTDN 563 PF-313 S. epidermidis YITSHKNARAIIKKFERDEILEEVITHYL 564 C. difficile NRK PF-314 S. mutans ECLKKAIKSKALNKAFKIDVPDEVYDN 565 LLMELEEYEK PF-317 S. mutans LILVSDI 566 PF-319 S. epidermidis SIGSMIGMYSFRHKTKHIKFTFGIPFILFL 567 B. subtilis QFLLVYFYILK C. difficile PF-320 S. mutans DSGYYALLENKEERVVWDGEVVANNI 568 E. coli FNNLWIVVNKVKTG PF-323 S. mutans ARESIEKSHVPVDATIVGVVDSFEVFDE 569 PF-324 C. difficile HFSLL 570 PF-325 S. mutans LTIDEKLRNHR 571 E. coli PF-326 S. mutans VIVGNLGAQKEKRNDTPISAKKDIMGD 572 E. coli KTVRVRADLHH PF-328 S. mutans NGNEKAFSEVENLVK 573 PF-329 S. epidermidis IGILFDKSVRKY 574 PF-333 S. mutans YMTKKLVEMAEQQMAGKSNR 575 PF-334 S. epidermidis QQYLILDRM 576 C. difficile PF-336 S. mutans MLTSRKKRLKKIVEEQNKKDESI 577 E. coli PF-337 S. epidermidis YMTKKLVEMAERQMAGK 578 PF-338 S. mutans KGTSCPDQLSKAIRQSI 579 PF-340 S. mutans VKDVLLELFNKIIGA 580 E. coli PF-344 B. subtilis DERLPEAKAIRNFNGSVMVLGR 581 C. jejuni PF-347 S. epidermidis GIFTGVTVVVSLKHC 582 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-348 B. subtilis ESASAAEWYNPNMNVKKAICMG 583 E. coli P. aeruginosa C. albicans E. faecalis C. jejuni PF-349 S. epidermidis MPKSCHVPVLCDFFFLVIIKFLALFKTIQ 584 B. subtilis S B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-350 S. epidermidis LAVILRAIVY 585 E. coli E. faecalis C. jeikeium C. jejuni PF-351 S. mutans YLFFKGKKVAEEEATKDEVKR 586 PF-352 C. jeikeium RVKKIG 587 PF-353 S. epidermidis EKTNFKGVKRNFYKKASFFV 588 M. luteus B. subtilis E. coli C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-354 S. epidermidis FTFSKCRASNGRGFGTLWL 589 B. subtilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-355 S. epidermidis WIAIGLLLYFSLKNQ 590 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-356 S. epidermidis VSIKIGAIVIGMIGLMELLTE 591 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-357 S. epidermidis MLTIIIGFIFWTMTLMLGYLIGEREGRK 592 M. luteus HE P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-358 S. epidermidis RNTAHNIKWRSKN 593 B. subtilis E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-359 S. epidermidis MTVMEDPGSEQRNKIQSPMKGEDFSAL 594 B. fragilis FGR P. aeruginosa C. albicans MRSA E. faecalis C. jeikeium PF-360 S. epidermidis MEQKVKVIFVPRSKPDNQLKTFVSAVL 595 B. subtilis FKA E. coli P. aeruginosa C. albicans E. faecalis C. jeikeium C. jejuni PF-361 S. epidermidis NQVTEGIRLLVE 596 E. coli E. faecalis C. jejuni PF-362 S. epidermidis NIERILKEKVWMIRCVE 597 E. coli P. aeruginosa C. albicans E. faecalis C. jejuni PF-363 B. subtilis SMLSVTVMCLMHASVAANQAMEKKV 598 E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis PF-364 S. epidermidis LVNGIKI 599 B. fragilis P. aeruginosa C. jeikeium C. jejuni PF-365 S. epidermidis LYKQKIQLEEELEKLKDDRQ 600 B. subtilis B. fragilis P. aeruginosa C. albicans PF-366 S. epidermidis ALCSVIKAIELGIINVHLQ 601 M. luteus B. fragilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-367 B. subtilis TKTPGTFTPGTGIQKTAVPL 602 PF-368 C. jeikeium MLKQTA 603 C. jejuni PF-369 B. subtilis MSEAVNLLRGARYSQRYAKNQVPYEVI 604 B. fragilis IEK E. coli P. aeruginosa C. albicans S. pneumoniae C. jeikeium C. jejuni PF-370 S. epidermidis VIFLHKESGNLKEIFY 605 E. coli P. aeruginosa E. faecalis C. jejuni PF-371 S. epidermidis TFIYNEF 606 B. fragilis C. jejuni PF-372 C. jeikeium KKQDKRIEDKYKRMKKGD 607 C. jejuni PF-373 S. epidermidis HFYLLFER 608 E. coli P. aeruginosa C. albicans MRSA E. faecalis C. jejuni PF-374 S. epidermidis HLFFVKGMFILCQKNQINDE 609 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-375 S. epidermidis MDSAKAQTMRTDWLAVSCLVASAYLR 610 B. subtilis SMLA B. fragilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-376 S. epidermidis MTVFEALMLAIAFATLIVKISNKNDKK 611 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-378 B. subtilis ESAKSNLNFLMQEEWALFLLL 612 B. fragilis E. coli P. aeruginosa C. jeikeium PF-379 S. epidermidis VFVVLFIIYLASKLLTKLFPIKK 613 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-380 S. epidermidis KKIIPLITLFVVTLVG 614 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-381 E. coli QGANPCQQVGFTVNDPDCRLAKTV 615 P. aeruginosa C. jejuni PF-382 S. epidermidis KYKCSWCKRVYTLRKDHKTAR 616 B. subtilis B. fragilis E. coli P. aeruginosa E. faecalis C. jeikeium C. jejuni PF-383 S. epidermidis WSEIEINTKQSN 617 B. subtilis B. fragilis E. coli C. jejuni PF-384 E. faecalis HISKERFEAY 618 C. jeikeium C. jejuni PF-385 S. epidermidis MIKKSILKIKYYVPVLISLTLILSA 619 E. coli P. aeruginosa C. albicans E. faecalis PF-386 S. epidermidis FTLTLITTIVAILNYKDKKK 620 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-387 B. subtilis GAVGIAFFAGNMKQDKRIADRQNKKSE 621 E. coli KK P. aeruginosa E. faecalis C. jeikeium C. jejuni PF-388 E. faecalis ITPLLDEIGKVCIDKISK 622 C. jeikeium C. jejuni PF-389 S. epidermidis GLQFKEIAEEFHITTTALQQWHKDNGY 623 C. albicans PIYNKNNRK MRSA S. pneumoniae E. faecalis C. jeikeium PF-390 S. epidermidis VVAYVITQVGAIRF 624 P. aeruginosa C. albicans MRSA PF-392 S. epidermidis DPAGCNDIVRKYCK 625 B. subtilis S. pneumoniae C. jeikeium C. jejuni PF-393 S. epidermidis DLVQSILSEFKKSG 626 E. coli C. albicans MRSA S. pneumoniae C. jejuni PF-394 S. epidermidis VLKEECYQKN 627 MRSA C. jejuni PF-395 S. epidermidis YCVPLGNMGNMNNKIW 628 E. coli P. aeruginosa S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-396 S. epidermidis LIYTILASLGVLTVLQAILGREPKAVKA 629 E. coli P. aeruginosa C. albicans E. faecalis C. jeikeium PF-397 S. epidermidis VEDLMEDLNA 630 MRSA S. pneumoniae E. faecalis C. jejuni PF-398 S. epidermidis ILVVLAGILLVVLSYVGISKFKMNC 631 B. subtilis B. fragilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-399 S. epidermidis FPIISALLGAIICIAIYSFIVNRKA 632 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jejuni PF-400 S. epidermidis VIAWKFRNKFENSGV 633 E. coli S. pneumoniae E. faecalis C. jeikeium PF-401 S. epidermidis YWLSRVTTGHSFAFEKPVPLSLTIK 634 E. coli P. aeruginosa MRSA E. faecalis C. jejuni PF-402 S. epidermidis FIDVLKSKINEFLN 635 P. aeruginosa E. faecalis C. jejuni PF-403 E. coli LLSTEQLLKYYDGETFDGFQLPSNE 636 P. aeruginosa S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-404 S. epidermidis VLYFQATVV 637 E. coli P. aeruginosa E. faecalis C. jeikeium C. jejuni PF-405 S. epidermidis LVRIEVDDLEEWYERNFI 638 E. coli E. faecalis PF-406 E. coli YLEMNADYLSNMDIFDELWEKYLENN 639 C. jejuni K PF-407 S. epidermidis KPKNKKEKTVISYEKLLSMY 640 B. subtilis E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-408 S. epidermidis YCVPLGNMGNMNNKIW 641 E. coli P. aeruginosa MRSA E. faecalis C. jeikeium C. jejuni PF-409 S. epidermidis DLVQSILSEFKKSG 642 MRSA C. jeikeium C. jejuni PF-410 S. epidermidis FALELIALCRNLFIVYFP 643 M. luteus B. fragilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-411 M. luteus WVAVAILLNIALQTQLT 644 B. subtilis B. fragilis P. mirabilis P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-412 M. luteus TSGWLGQLEQ 645 E. coli C. albicans C. jeikeium C. jejuni PF-413 P. aeruginosa TFAGSIKIGVPDLVHVTFNCKR 646 C. albicans C. jejuni PF-414 E. coli LLNKKLE 647 C. albicans C. jeikeium PF-416 S. pneumoniae SKAGLYGKIERSDKRE 648 C. jeikeium PF-417 S. epidermidis DSYFRS 649 C. jeikeium C. jejuni PF-418 S. epidermidis FFLVHFYIRKRKGKVSIFLNYF 650 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-421 C. jeikeium KHCFEITDKTDVV 651 PF-422 C. albicans MSRKKYENDEKSQKKLKIGRKSDVFYG 652 MRSA IID C. jeikeium PF-423 S. epidermidis AGKKERLLSFREQFLNKNKKK 653 M. luteus E. coli S. pneumoniae E. faecalis C. jeikeium PF-424 S. epidermidis IAAFVTSRAFSDTVSPI 654 C. albicans MRSA PF-425 S. epidermidis MMELVLKTIIGPIVVGVVLRIVDKWLN 655 M. luteus KDK E. coli P. aeruginosa C. albicans MRSA S. pneumoniae C. jeikeium PF-426 S. epidermidis MLQKYTQMISVTKCIITKNKKTQENVD 656 E. coli AYN P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-427 M. luteus YVLEYHGLRATQDVDAFMAL 657 P. aeruginosa C. albicans C. jejuni PF-428 S. epidermidis ENEESIF 658 C. albicans E. faecalis C. jeikeium PF-429 S. epidermidis AATLICVGSGIMSSL 659 S. pneumoniae C. jeikeium PF-430 S. epidermidis AVVCGYLAYTATS 660 M. luteus E. coli S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-431 S. epidermidis VAYAAICWW 661 M. luteus E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-432 S. epidermidis FNGDSEFFLCIAF 662 M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-433 S. epidermidis MRKEFHNVLSSGQLLADKRPARDYNR 663 E. coli K S. pneumoniae C. jeikeium PF-434 S. epidermidis GQLLADKRPARDYNRK 664 M. luteus S. pneumoniae C. jeikeium PF-435 C. jeikeium MSRWDGHSDKGEAPAGKPPMHGFGLN 665 GENK PF-436 C. jeikeium KKHVLVGKQEKNG 666 PF-438 S. epidermidis QPYFQNQFKKITGYTPLQYRKEKR 667 E. coli S. pneumoniae C. jeikeium C. jejuni PF-439 S. epidermidis RVLVLKKFHGIMDGNRNVAVFFVGQ 668 M. luteus B. fragilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-440 S. epidermidis MFIISPDLFNIAVILYILFFIHDILLLILS 669 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-441 C. jeikeium TQVHKMARGIDPGPANGIYR 670 PF-442 S. epidermidis MQIFYIKTKIFLSFFLFLLIFSQCFYKIEE 671 E. coli C. albicans S. pneumoniae E. faecalis PF-443 S. epidermidis KLLYFFNYFENLQQVHLLVQL 672 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-444 M. luteus MAAKLWEEGKMVYASSASMTKRLKL 673 C. albicans AMSKV S. pneumoniae C. jeikeium PF-445 M. luteus ASMTKRLKLAMSKV 674 S. pneumoniae C. jeikeium PF-446 M. luteus SGNEKV 675 C. jeikeium PF-447 S. epidermidis IDKSRNKDQFSHIFGLYNICSG 676 M. luteus E. coli S. pneumoniae PF-448 S. epidermidis SLQSQLGPCLHDQRH 677 M. luteus P. mirabilis E. coli S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-450 S. epidermidis HRNLIILQRTIFI 678 M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-451 S. epidermidis MVNYIIGSYMLYREQNNNEALRKFDIT 679 M. luteus LAM E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-452 M. luteus MNNWIKVAQISVTVINEVIDIMKEKQN 680 P. aeruginosa GGK C. albicans S. pneumoniae E. faecalis C. jeikeium M. smegmatis PF-453 M. luteus IIQDIAHAFGY 681 E. coli P. aeruginosa S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-454 S. epidermidis MSVFVPVTNIFMFIMSPIFNVNLLHFKV 682 M. luteus YI E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-456 C. albicans TCVKPRTIN 683 MRSA E. faecalis C. jeikeium C. jejuni PF-457 C. albicans INKYHHIA 684 S. pneumoniae E. faecalis C. jeikeium PF-458 S. epidermidis ISLIIFIMLFVVALFKCITNYKHQS 685 M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-459 P. aeruginosa EKRMSFNENQSHRPLL 686 PF-460 S. epidermidis MEHVLPFQNTPPNIVIIYKDFTHLKSITF 687 M. luteus S P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-461 E. coli MTLAIKNCSVTKCLGFGDFVNDDSDSY 688 S. pneumoniae FDA PF-462 E. faecalis KNKTDTL 689 C. jeikeium PF-463 S. epidermidis MVILVFSLIFIFTDNYLVYQSKSIKEDVM 690 E. coli I P. aeruginosa C. albicans S. pneumoniae E. faecalis M. smegmatis PF-464 S. epidermidis VDMVNRFLGN 691 C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-465 S. epidermidis KPVGKALEEIADGKIEPVVPKEYLG 692 M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-466 MRSA VRKSDQ 693 C. jeikeium C. jejuni PF-467 MRSA YYKDYFKEI 694 E. faecalis C. jeikeium C. jejuni PF-469 S. epidermidis YKVNYNNIDNHFNTLRH 695 M. luteus P. mirabilis E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-470 M. luteus PYSDSYATRPHWEQHRAR 696 E. coli MRSA E. faecalis C. jeikeium C. jejuni PF-471 S. epidermidis MVGKIRGVTPRNDLLNANITGQLNLNY 697 M. luteus RLI E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-472 S. epidermidis MHISHLLDEVEQTEREKAVNVLENMNG 698 E. coli NVI P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-473 S. epidermidis MAADIISTIGDLVKWIIDTVNKFKK 699 E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-474 S. epidermidis MHRNLVLVKMEPIPHIMIIANQIGIIIEKA 700 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-475 S. epidermidis MREKVRFTQAFKLFWTNYFNFKGRSRR 701 M. luteus SEY P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-476 M. luteus WADAQYKLCENCSE 702 P. mirabilis C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-477 S. epidermidis HKNKLNIPHIKS 703 M. luteus C. albicans S. pneumoniae C. jeikeium C. jejuni PF-478 S. epidermidis HLFILKSHLKPFPPFRYTYD 704 M. luteus P. mirabilis E. coli C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-479 S. epidermidis AYILKRREEKNK 705 M. luteus P. mirabilis E. coli C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-480 S. epidermidis MVEILVNTAISVYIVALYTQWLSTRDNL 706 M. luteus KA P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-481 C. jeikeium DELYEIMDKVIEEFNKDIEQNNNNGNN 707 EDLTENKIN PF-482 S. epidermidis LVGYVRTSGTVRSYKIN 708 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-483 P. mirabilis EDNKDKKDKKDK 709 C. jeikeium C. jejuni PF-484 S. epidermidis HKKDIRKQVFKN 710 M. luteus P. mirabilis E. coli E. faecalis C. jeikeium C. jejuni PF-486 S. mutans MQKEGEEDY 711 PF-487 S. mutans MYKAIAVLAMTIMAFFIFVYPFFIVGLIL 712 E. coli G PF-488 S. mutans YPNEQGHHKNNLKNIIIE 713 E. coli PF-489 S. mutans KVDRVSTTITEKIK 714 PF-490 S. mutans RLILVSGNATVQK 715 E. coli PF-491 S. mutans IHQYSSKPDIVGQEAKTVQQINS 716 E. coli PF-492 S. mutans IQIDAASFYSISKSTIK 717 B. subtilis E. coli PF-493 S. mutans PGAFFFCRGRGCWCGIGW 718 B. subtilis E. coli PF-494 S. mutans FTEPLRPLQAKGQIISIKPSTSSS 719 PF-495 S. mutans KGIYKKRTY 720 E. coli PF-496 S. mutans EVTKRLVALAQQQLRG 721 E. coli PF-497 S. mutans LVLRICTDLFTFIKWTIKQRKS 722 B. subtilis E. coli PF-498 S. mutans MSEEEEVSEKVYNYLRRNEFFEVRKEE 723 E. coli FSA PF-499 S. mutans VYSFLYVLVIVRKLLSMKKRIERL 724 E. coli PF-500 S. mutans MGIFKEEKIKFIDCKGEEVILKIKIKDIKK 725 E. coli PF-501 S. mutans GSTAHKSPIGSTNNQWGMKKTPTD 726 PF-502 S. mutans NKGKQMQDQTGKQPIVDNG 727 PF-503 S. mutans VVTLKDIVAVIEDQGYDVQ 728 PF-504 S. mutans ILSVELSTKTSASGS 729 E. coli PF-505 S. mutans GYTKDPGTGI 730 PF-506 S. mutans SGRGFALIVVLFILLIIVGAACIR 731 E. coli PF-507 S. mutans LALSIANLFKKKA 732 E. coli PF-508 S. mutans VSTFGKVVKVVDEK 733 PF-509 S. mutans EAKVQAKGEQIACNNY 734 B. subtilis E. coli PF-510 S. mutans WYLYKKQSNQNDRGIPK 735 E. coli PF-511 E. coli VMQSLYVKPPLILVTKLAQQN 736 P. aeruginosa S. pneumoniae C. jeikeium PF-512 S. pneumoniae SFMPEIQKNTIPTQMK 737 C. jeikeium PF-513 C. albicans SNGVGLGVGIGSGIRF-NH2 738 PF-514 S. epidermidis QRFYKLFYHIDLTNEQALKLFQVK 739 E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-515 S. epidermidis DKSTQDKDIKQAKLLAQELGL-NH2 740 C. albicans S. pneumoniae C. jeikeium PF-517 C. jejuni VKPTMTASLISTVC 741 PF-518 S. epidermidis SFYSKYSRYIDNLAGAIFLFF 742 E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-519 M. luteus YLVYSGVLATAAAF-NH2 743 E. faecalis C. jeikeium PF-520 S. epidermidis LGLTAGVAYAAQPTNQPTNQPTNQPTN 744 M. luteus QPTNQPTNQPRW-NH2 E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-521 S. epidermidis CGKLLEQKNFFLKTR 745 E. coli P. aeruginosa S. pneumoniae E. faecalis PF-522 S. epidermidis FELVDWLETNLGKILKSKSA-NH2 746 E. coli P. aeruginosa S. pneumoniae E. faecalis PF-523 S. epidermidis ASKQASKQASKQASKQASKQASRSLKN 747 M. luteus HLL C. albicans S. pneumoniae C. jeikeium C. jejuni PF-524 S. epidermidis PDAPRTCYHKPILAALSRIVVTDR 748 E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-526 S. epidermidis VLLLFIFQPFQKQLL-NH2 749 E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-527 S. epidermidis GSVIKKRRKRMAKKKHRKLLKKTRIQR 750 M. luteus RRAGK P. mirabilis E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-528 S. epidermidis LVDVVVLIRRHLPKSCS-NH2 751 P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-529 S. epidermidis LSEMERRRLRKRA-NH2 752 E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-537 S. epidermidis LANDYYKKTKKSW 753 M. luteus P. mirabilis E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-539 S. epidermidis SIILTKKKRRKIPLSIDSQIYKYTFKQ 754 M. luteus B. subtilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-540 C. albicans KSILILIKVIFIGQTTIIL 755 PF-542 C. jeikeium KKDNPSLNDQDKNAVLNLLALAK 756 PF-543 S. epidermidis NILFGIIGFVVAMTAAVIVTAISIAK 757 M. luteus B. subtilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-544 S. epidermidis FGEKQMRSWWKVHWFHP 758 M. luteus P. mirabilis P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-545 S. epidermidis RESKLIAMADMIRRRI-NH2 759 E. coli P. aeruginosa S. pneumoniae E. faecalis C. jeikeium PF-546 S. epidermidis PIIAPTIKTQIQ 760 E. coli C. albicans S. pneumoniae E. faecalis C. jeikeium PF-547 S. epidermidis WSRVPGHSDTGWKVWHRW-NH2 761 E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-548 M. luteus ARPIADLIHFNSTTVTASGDVYYGPG 762 P. mirabilis E. coli P. aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-549 E. coli TGIGPIARPIEHGLDS 763 C. albicans S. pneumoniae C. jeikeium PF-550 S. pneumoniae STENGWQEFESYADVGVDPRRYVPL 764 PF-551 S. pneumoniae QVKEKRREIELQFRDAEKKLEASVQAE 765 PF-552 S. pneumoniae ELDKADAALGPAKNLAPLDVINRS 766 PF-553 S. epidermidis LTIVGNALQQKNQKLLLNQKKITSLG 767 E. coli P. aeruginosa C. albicans MRSA S. pneumoniae C. jeikeium PF-554 S. pneumoniae AKNFLTRTAEEIGEQAVREGNINGP 768 PF-555 MRSA EAYMRFLDREMEGLTAAYNVKLFTEAI 769 S. pneumoniae S C. jeikeium PF-556 S. epidermidis SLQIRMNTLTAAKASIEAA 770 M. luteus B. fragilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-557 S. pneumoniae AANKAREQAAAEAKRKAEEQAR 771 PF-558 S. epidermidis ADAPPPLIVRYS 772 E. coli C. albicans C. jeikeium C. jejuni PF-559 S. epidermidis SRPGKPGGVSIDVSRDRQDILSNYP 773 M. luteus C. albicans C. jeikeium C. jejuni PF-560 S. epidermidis FGNPFRGFTLAMEADFKKRK 774 M. luteus E. coli S. pneumoniae C. jeikeium C. jejuni PF-562 S. epidermidis TPEQWLERSTVVVTGLLNRK 775 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-563 S. epidermidis RPELDNELDVVQNSASLDKLQASYN 776 M. luteus C. jeikeium PF-564 S. epidermidis TIILNDQINSLQERLNKLNAETDRR 777 C. albicans S. pneumoniae C. jeikeium PF-566 P. mirabilis EAQQVTQQLGADFNAITTPTATKV 778 S. pneumoniae PF-567 S. epidermidis QQRVKAVDASLSQVSTQVSGAVASA 779 P. aeruginosa C. albicans MRSA S. pneumoniae C. jeikeium PF-568 S. epidermidis TQAVQVKTAQAQQQ 780 PF-569 M. luteus KSKISEYTEKEFLEFVEDIYTNNK 781 P. mirabilis S. pneumoniae E. faecalis C. jeikeium PF-570 S. pneumoniae KKFPTEESHIQAVLEFKKLTEHPSG 782 C. jeikeium PF-572 S. epidermidis WRASKGLPGFKAG 783 M. luteus E. coli S. pneumoniae C. jeikeium PF-573 S. epidermidis EKKLIVKLIDSIGKSHEEIVGAG 784 S. pneumoniae PF-575 M. luteus LNFRAENKILEKIHISLIDTVEGSA 785 E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-576 M. luteus AYSGELPEPLVRKMSKEQVRSVMGK 786 P. mirabilis E. coli P. aeruginosa C. albicans S. pneumoniae PF-577 S. epidermidis PFETRESFRVPVIGILGGWDYFMHP 787 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-578 S. epidermidis QKANLRIGFTYTSDSNVCNLTFALLGSK 788 M. luteus P. mirabilis P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-579 S. epidermidis MILVCAAVIWGRVLFILKFPIYFSIRLAF 789 M. luteus L P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-580 S. epidermidis EILNNNQVIKELTMKYKTQFESNLGGW 790 M. luteus TARARR E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-581 S. epidermidis WTARARR 791 M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-583 S. epidermidis KFQGEFTNIGQSYIVSASHMSTSLNTGK 792 M. luteus E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-584 S. epidermidis SYIKNLSNQKFLIAF 793 M. luteus P. mirabilis C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-585 S. epidermidis DYNHLLNVVQDWVNTN 794 E. coli C. albicans MRSA S. pneumoniae C. jeikeium PF-586 S. epidermidis FFNQANYFFKEF 795 M. luteus E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-587 S. epidermidis ASGKYQSYLLNVYVDSKKDRLDIFDKL 796 M. luteus KAKAKFVL E. coli MRSA S. pneumoniae E. faecalis C. jeikeium PF-588 S. epidermidis ESVEAIKAKAIK 797 E. coli C. albicans E. faecalis C. jeikeium C. jejuni PF-589 S. epidermidis APLRIDEIRNSNVIDEVLDCAPKKQEHFF 798 C. albicans VVPKIIE MRSA S. pneumoniae PF-590 S. epidermidis YYQAKLFPLL 799 M. luteus E. coli E. faecalis C. jeikeium PF-592 S. epidermidis IMKNYKYFKLFIVKYALF 800 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-593 C. jeikeium MEISTLKKEKLHVKDELSQYLANYKK 801 PF-594 C. jeikeium IVSAIV 802 PF-595 S. epidermidis LQNKIYELLYIKERSKLCS 803 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-596 S. epidermidis SKMWDKILTILILILELIRELIKL 804 M. luteus P. mirabilis E. coli P. aeruginosa MRSA E. faecalis C. jeikeium C. jejuni PF-597 P. mirabilis DEIKVSDEEIEKFIKENNL 805 PF-598 S. epidermidis MKFMLEVRNKAISAYKEITRTQI 806 M. luteus P. mirabilis P. aeruginosa C. albicans MRSA S. pneumoniae C. jeikeium PF-599 S. epidermidis LFEIFKPKH 807 P. mirabilis E. coli C. albicans MRSA S. pneumoniae C. jeikeium PF-600 S. epidermidis TKKIELKRFVDAFVKKSYENYILERELK 808 M. luteus KLIKAINEELPTK B. subtilis P. mirabilis E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium PF-601 C. jeikeium YRVTVKALE 809 PF-602 P. mirabilis LEKEKKEYIEKLFKTK 810 C. jeikeium PF-603 S. epidermidis IDKLKKMNLQKLSYEVRISQDGKSIYAR 811 M. luteus IK B. subtilis E. coli P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium PF-604 S. epidermidis LMEQVEV 812 C. albicans C. jeikeium PF-605 S. epidermidis HYRWNTQWWKY 813 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-607 S. epidermidis YIESDPRKFDYIFGAIRDH 814 P. mirabilis E. coli MRSA S. pneumoniae C. jeikeium PF-609 P. mirabilis TEIKLDNNEYLVLNLDDILGILK 815 E. coli S. pneumoniae PF-610 S. epidermidis VFLKLKTSKIDLASIIFYP 816 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni PF-612 S. epidermidis GTTLKYGLERQLKIDIHPEITIINLNGGA 817 M. luteus DEFAKL P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-613 C. jeikeium ADEFAKL 818 PF-614 S. epidermidis GLDIYA 819 E. coli C. jeikeium PF-615 S. epidermidis FLNRFIFYIFTVKTKSALIKNLFLD 820 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae C. jeikeium C. jejuni PF-616 C. jeikeium IVFVVTKEKK 821 PF-617 P. aeruginosa PMNAAEPE 822 C. albicans PF-619 S. epidermidis WSRVPGHSDTGWKVWHRW 823 M. luteus B. subtilis P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-621 S. epidermidis PPSSFLV 824 C. albicans PF-622 S. epidermidis TREDVFSVRLINNIVNKQA 825 P. aeruginosa C. albicans S. pneumoniae E. faecalis C. jeikeium PF-623 S. epidermidis VLFAVYLGALDWLFSWLTQKM 826 P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium PF-625 S. epidermidis SDSTNNARTRKKARDVTTKDIDK 827 M. luteus S. pneumoniae C. jeikeium PF-626 S. epidermidis KYDFDDFEPEEA 828 M. luteus E. coli C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-627 S. epidermidis INDLLSYFTLHEK 829 P. aeruginosa MRSA S. pneumoniae E. faecalis C. jeikeium PF-629 S. epidermidis GLAAIATVFALY 830 P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-630 S. epidermidis IPATPIIHS 831 M. luteus P. mirabilis P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-631 S. epidermidis LIIYFSKTGNTARATRQI 832 P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-632 S. epidermidis TTIQGVASLEKHGFRYTIIYPTRI 833 P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-634 S. epidermidis MPKARPVNHNKKKSKITIKSNFTLFYM 834 M. luteus FNP P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-635 S. epidermidis MNAHGHSLIFQKMIVHAFAFFSKQKNY 835 P. aeruginosa LYF C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-636 S. epidermidis LVRLA 836 C. albicans MRSA S. pneumoniae E. faecalis PF-637 S. epidermidis SRIKQDARSVRKYDRIGIFFYSFKSA 837 P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-638 S. epidermidis TFILPK 838 C. albicans MRSA C. jeikeium PF-639 S. pneumoniae QATQIKSWIDRLLVSED 839 C. jeikeium PF-640 C. albicans MGDINRNF 840 PF-641 S. epidermidis SWKCHHLAIGGSWKCHHLAI 841 M. luteus E. coli C. albicans MRSA E. faecalis C. jeikeium C. jejuni PF-642 M. luteus FTTPMIGIPAGLLGGSYYLKRREEKGK 842 MRSA C. jeikeium PF-643 Mycobacteria spp VRCRL 843 PF-644 Mycobacteria spp TSGLIIGENGLNGL 844 PF-645 Mycobacteria spp SNSVQQG 845 PF-646 Mycobacteria spp APASPGRRPG 846 PF-647 Mycobacteria spp GTFLGQKCAAATAS 847 PF-648 S. mutans ARRYPAAGS 848 E. coli PF-649 Mycobacteria spp CPRYPFVDVGPAGPWRARWRVGS 849 PF-650 Mycobacteria spp IRSDQPGRQSRSSPRWPTGAGRHR 850 PF-651 Mycobacteria spp PRWPTGAGRHR 851 PF-652 Mycobacteria spp FLAPARPDLQAQRQALAQ 852 PF-653 Mycobacteria spp QSVHPLPAETPVADVI 853 PF-654 Mycobacteria spp LSGRLAGRR 854 PF-655 M. smegmatis DAPCFDDQFGDLKCQMC 855 PF-656 Mycobacteria spp RGMFVPFHDVDCVQ 856 PF-657 Mycobacteria spp YVANYTITQFGRDFDDRLAVAIHFA 857 PF-658 Mycobacteria spp PTTPPPTTPPEIPTGGTVIST 858 PF-659 Mycobacteria spp TVIST 859 PF-660 Mycobacteria spp TDPQATAAPRRRTSPR 860 PF-661 Mycobacteria spp PDEDIRRRAILPPAGPCRPMSPE 861 PF-662 Mycobacteria spp GKQSRAHGPVASRREFRRKSG 862 PF-663 Mycobacteria spp ATLIPRKA 863 PF-664 M. smegmatis DQLCVEYPARVSTG 864 PF-665 Mycobacteria spp VLRVATAVGEVPTGL 865 PF-666 Mycobacteria spp PNRRSRPR 866 PF-667 Mycobacteria spp PAHQRLRIDQRLVADRDMVQDYES 867 PF-668 Mycobacteria spp TNAESMALAFRGRVHMSVNIAGLT 868 PF-669 Mycobacteria spp RADRIESYPADGDRVITLWRNPYR 869 PF670 Mycobacteria spp TVIVAPMHSGV 870 PF-671 S. mutans TVSAFRTVH 871 E. coli PF-673 S. mutans VRRLRM 872 E. coli PF-674 S. mutans DGCDSEPALTYR 873 E. coli PF-675 Mycobacteria spp EIIPISPTRRCEMHTMSSAEYRGL 874 PF-676 S. mutans AEYRGL 875 E. coli PF-677 Mycobacteria spp TCRGAGMH 876 PF-678 Mycobacteria spp RDRRWTRRDMYDWLESARV 877 PF-679 S. mutans CRARFIRR 878 E. coli PF-680 Mycobacteria spp ADPHPTTGI 879 PF-681 M. smegmatis TALTTVGVSGARLITYCVGVEDI 880 PF-682 Mycobacteria spp RRGKSEQGLSRR 881 PF-683 Mycobacteria spp LWPVA 882 PF-684 Mycobacteria spp RKLSLASGFALWRRSLV 883 PF-685 Mycobacteria spp PTLWLACL 884 PF-686 M. smegmatis LAVLMGYIGYRGWSGKRHINRQ 885 PF-687 Mycobacteria spp AKRVLSLAVAPHRRQPVQGT 886 PF-688 Mycobacteria spp ARNHAVIPAG 887 PF-689 S. mutans SAPSG 888 E. coli PF-690 Mycobacteria spp MIPLAGDPVSSHRTVEFGVLGTYLVSG 889 GSL PF-691 Mycobacteria spp HRTVEFGVLGTYLVSGGSL 890 PF-692 Mycobacteria spp GVAREDPLEPDPLAPIIDDSR 891 PF-693 Mycobacteria spp PDPAR 892 PF-694 Mycobacteria spp DLIRPLYSMSAPSVA 893 PF-695 Mycobacteria spp ALSVMLGNIPLVVPNANQL 894 PF-696 Mycobacteria spp IRSGISAAYARPLR 895 PF-697 Mycobacteria spp RADARAK 896 PF-698 Mycobacteria spp SSGRAGVKCRRPTGR 897 PF-699 Mycobacteria spp GRAGVKCRRPTGR 898 PF-700 Mycobacteria spp LNWPFTGR 899 PF-701 S. mutans PRGAQSGHG 900 PF-702 Mycobacteria spp LSGRLAGRR 901 PF-703 Mycobacteria spp MTTVDNIVGLVIAVALMAFLFAALLFPE 902 KF PF-704 Mycobacteria spp APAARAAL 903 PF-705 S. mutans GEEEGTVAD 904 E. coli PF-706 L. pneumophila LGYGAWIGCGLGLNGFHRID 905 PF-707 S. mutans IDPESIVTTNNKQDNVDEQ 906 E. coli PF-709 S. mutans NKKHSPMD 907 PF-711 S. mutans KTAGPTGTIYKTN 908 PF-712 S. mutans QIYRHVHKVQAKSANLRLY 909 E. coli PF-714 L. pneumophila FVVTQRMLRMYKK 910 PF-716 S. mutans HGENHHHKSDEKDNDSSEKKD 911 PF-717 E. coli PQSEVTFENIYAPKANGGGLYGI 912 PF-720 S. mutans SLDMGK 913 PF-724 L. pneumophila CYRFLTPKRPTRIS 914 PF-727 S. mutans AYARCRHDYPFTLGQMQTH 915 E. coli PF-728 S. mutans AIGQEQDRREYYYYSGYPYYY 916 E. coli PF-731 L. pneumophila RHKLIRLPLSESVFCFLNNPKI 917 PF-732 E. coli DRPSQTTHHTLSSSRITGPS 918 PF-733 S. mutans VISRQMGSEAVLELFIIM 919 E. coli PF-735 S. mutans YDPLFPNDKN 920 E. coli PF-737 S. epidermidis KSSGSSASASSTAGGSSSK 921 S. pneumoniae PF-738 S. epidermidis KSGATSAASGAKSGASS 922 C. albicans C. jeikeium PF-741 S. epidermidis AKREDTVAAQIGANILNLIQ 923 M. luteus P. mirabilis P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-744 S. epidermidis LGVGTFVGKVLIKNQQKQKSKKKAQ 924 M. luteus E. coli MRSA S. pneumoniae E. faecalis C. jeikeium PF-745 S. epidermidis ANSQNSLFSNRSSFKSIFDKKSNITTNAT 925 M. luteus TPNSNIIIN C. albicans PF-746 S. epidermidis FLGNSQYFTRK 926 M. luteus E. coli C. albicans S. pneumoniae E. faecalis C. jeikeium PF-748 S. epidermidis FQGFFDVAVNKWWEEHNKAKLWKNV 927 M. luteus KGKFLEGEGEEEDDE E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-749 S. epidermidis GVNKWWEEHNKAKLWKNVKGKFLEG 928 M. luteus EGEEEDDE E. coli P. aeruginosa C. albicans S. pneumoniae C. jeikeium PF-750 M. luteus AESSPAKTTA 929 C. jeikeium PF-751 S. epidermidis AESSPAQETT 930 E. coli C. albicans C. jeikeium PF-752 S. epidermidis LHVIRPRPELSELKFPITKILKVNKQGLK 931 E. coli K MRSA S. pneumoniae E. faecalis PF-756 S. epidermidis DALLRLA 932 M. luteus C. albicans MRSA C. jeikeium PF-757 M. luteus PQAISSVQQNA 933 C. albicans MRSA PF-758 S. epidermidis PEIIKIVSGLL 934 M. luteus E. coli MRSA S. pneumoniae E. faecalis C. jeikeium PF-760 S. epidermidis DHITLDDYEIHDGFNFELYYG 935 M. luteus PF-761 S. epidermidis SKFELVNYASGCSCGADCKCASETECK 936 M. luteus CASKK P. mirabilis P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis PF-762 M. luteus PAPAPSAPAPAPEQPEQPA 937 C. albicans PF-763 S. epidermidis GIWMARNYFHRSSIRKVYVESDKEYER 938 M. luteus VHPMQKIQYEGNYKSQ E. coli C. albicans MRSA S. pneumoniae E. faecalis PF-764 S. epidermidis GYFEPGKRD 939 M. luteus C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-765 S. epidermidis YLYWEVEHKPIIAKRDAYYAQLRKQKE 940 M. luteus IEEGA E. coli MRSA E. faecalis C. jeikeium PF-766 S. epidermidis DAYYAQLRKQKEIEEGA 941 M. luteus C. albicans MRSA E. faecalis C. jeikeium PF-767 S. epidermidis DGKQGEPVALKPTDN 942 M. luteus E. coli MRSA S. pneumoniae E. faecalis C. jeikeium PF-768 S. epidermidis GFRGGKRGGARG 943 S. pneumoniae E. faecalis C. jeikeium PF-770 S. epidermidis GVGIGFIMMGVVGYAVKLVHIPIRYLIV 944 M. luteus P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium PF-772 S. epidermidis TKESSS 945 C. albicans MRSA S. pneumoniae C. jeikeium PF-773 S. epidermidis TLKESK 946 C. albicans C. jeikeium PF-776 S. epidermidis VSILLYLSATIILPNVLRLLVARAIIVRV 947 M. luteus P. mirabilis C. albicans MRSA S. pneumoniae E. faecalis PF-777 Mycobacteria spp. PGADGKLAEASAAIARLVRS 948 PF-778 Mycobacteria spp. MNLILTAHGT 949 PF-779 Mycobacteria spp. IYGDFFNFYLCDISLKVNGLQPGGPVRT 950 VKLFGQPTGRCTPQ PF-780 Mycobacteria spp. AVYDALVALAAAEHRAELATRDARAK 951 DTYEKIGVHVVVAA PF-781 Mycobacteria spp. PLVVVNHRRAERSRG 952 PF-782 Mycobacteria spp. TGPRRGIDLTSNRALSEVLDEGLELNSR 953 K PF-783 Mycobacteria spp. FT SEVRGVFTYRVNKAGLITNMRGYW 954 NLDMMTFGNQE PF-784 Mycobacteria spp. MAMTTVDNIVGLVIAVALMAFLFAALL 955 FPEKF PF-785 Mycobacteria spp. MRPQHSPAGKAFVVKKITHEQS 956 PF-786 Mycobacteria spp. LSERERRRLKRGII 957 PF-787 Mycobacteria spp. MTERQRRALLKQHPEVVSWSDYLEKR 958 KRRTGTAG PF-788 Mycobacteria spp. GLITVFAGTARILQLRRAAKKTHAAAL 959 R PF-789 Mycobacteria spp. PRGAQSGHG 960 PF-790 Mycobacteria spp. PAGPDHLDQRDHR 961 PF-791 S. mutans IFLTTQNTDYSEHNAA 962 PF-792 S. mutans ALHASGIQAI 963 PF-793 S. mutans YTQUNNASAYAMLLTNKDTVP 964 PF-794 S. mutans NLYFENQGN 965 PF-795 S. mutans ALHKSGIQVIADWVPDQIYN 966 PF-796 S. mutans YTQSNIPTAYALMLSNKDSI 967 PF-797 S. mutans WYYFDNNGYM 968 PF-798 S. mutans ALHSKGIKVMADWVPDQMYA 969 PF-799 S. mutans YTHYNTALSYALLLTNKSSVP 970 PF-800 S. mutans WYYFDNNGYM 971 PF-C003 A. naeslundii FCSVDHDVITIAADHVKQGAEA 972 P. gingivalis S. mutans PF-C008 A. naeslundii AQPRRTWLVNFGEVPSPGLTNDGMPDH 973 PF-C034 S. mutans HPMPITVRSRKPGPLTAPSEH 974 E. coli PF-C045 A. naeslundii FREGMGWPLSNEGSPTAPLPKHRNQV 975 T. denticola PF-C050 A. naeslundii QGLARPVLRRIPL 976 S. mutans PF-C052 A. naeslundii SRFRNGV 977 F. nucleatum S. mutans PF-C055 A. naeslundii YNLSIYIYFLHTITIAGLITLPFII 978 F. nucleatum P. gingivalis S. mutans PF-C057 A. naeslundii YFWWYWVQDCIPYKNNEVWLELSNN 979 F. nucleatum MK P. gingivalis S. mutans PF-C058 A. naeslundii FETGFGDGYYMSLWGLNEKDEVCKVV 980 F. nucleatum IPFINPELID P. gingivalis S. mutans PF-C061 A. naeslundii TLNYKKMFFSVIFLLGLNYLICNSPLFFK 981 F. nucleatum QIEF P. gingivalis S. mutans T. denticola PF-C062 A. naeslundii PLARATEVVATLFIICSLLLYLTR 982 F. nucleatum P. gingivalis S. mutans T. denticola PF-C063 A. naeslundii SHFRKGD 983 F. nucleatum S. mutans PF-C064 A. naeslundii DEEALEMGANLYAQFAIDFLNSKK 984 F. nucleatum P. gingivalis S. mutans T. denticola PF-C065 A. naeslundii DEERYSDSYFLKEKVFYLILALFLILFHQ 985 F. nucleatum KYLYFLEIITI P. gingivalis S. mutans PF-C068 A. naeslundii LNLFASI 986 F. nucleatum S. mutans PF-C069 A. naeslundii NALMLREMQLAKNIKVEVTDVLSNKK 987 F. nucleatum YC P. gingivalis S. mutans T. denticola PF-C071 A. naeslundii QVIVKIL 988 F. nucleatum S. mutans PF-C072 A. naeslundii KKMFSLIRKVNWIFFILFIVLDLTNVFPLI 989 F. nucleatum RTILFAILSRQ P. gingivalis S. mutans T. denticola PF-C075 A. naeslundii KALVISVFAIVFSIIFVKFFYWRDKK 990 F. nucleatum P. gingivalis S. mutans T. denticola PF-C080 A. naeslundii INIPGLF 991 F. nucleatum S. mutans PF-C084 A. naeslundii FFSVIFLFGLNYLICNSPLFNILR 992 F. nucleatum P. gingivalis S. mutans PF-C085 A. naeslundii KKFKIFVIINWFYHKYIILNFEENF 993 F. nucleatum P. gingivalis S. mutans T. denticola PF-C086 A. naeslundii ELFFTILSDCNELFLLHLLQQPLFYIKKG 994 F. nucleatum K P. gingivalis S. mutans T. denticola PF-C088 A. naeslundii DIANNILNSVSERLIIA 995 F. nucleatum P. gingivalis S. mutans T. denticola PF-C091 A. naeslundii ASNTPRFVRLTLFNFYSKIWNVTHLFLF 996 F. nucleatum NNL P. gingivalis S. mutans T. denticola PF-C093 A. naeslundii EKLGTMV 997 F. nucleatum S. mutans PF-C095 A. naeslundii LLALNMNEDTYYFELFFIFDNQNKKWL 998 F. nucleatum IFDLKERG P. gingivalis S. mutans PF-C098 A. naeslundii PETKGKVSAFVFGIVVANVIAVVYILYM 999 F. nucleatum LREIGIIQ P. gingivalis S. mutans T. denticola PF-C120 A. naeslundii ASLSTMTFKVMELKELIILLCGLTMLMI 1000 F. nucleatum QTEFV P. gingivalis S. mutans T. denticola PF-C131 A. naeslundii QWIVAKREIRMHIYCHISVIHVIIFFG 1001 F. nucleatum P. gingivalis S. mutans PF-C134 A. naeslundii NELMKYPATLTATATTPGIKYSHLCSVC 1002 F. nucleatum L P. gingivalis S. mutans T. denticola PF-C135 A. naeslundii KNTHAYLRVLRLSSLILSYQASVYPLFA 1003 F. nucleatum YLCQQKDY P. gingivalis S. mutans PF-C136 A. naeslundii LILSYQASVYPLFAYLCQQKDY 1004 F. nucleatum P. gingivalis S. mutans T. denticola PF-C137 A. naeslundii QRMYWFKRGFETGDFSAGDTFAELK 1005 F. nucleatum P. gingivalis S. mutans PF-C139 A. naeslundii LLASHPERLSLGVFFVYRVLHLLLENT 1006 F. nucleatum P. gingivalis S. mutans T. denticola PF-C142 A. naeslundii DFPPLSFFRRRFHAYTAPIDNFFGANPF 1007 F. nucleatum P. gingivalis S. mutans T. denticola PF-C143 A. naeslundii VVFGGGDRLV 1008 F. nucleatum P. gingivalis S. mutans T. denticola PF-C145 A. naeslundii YGKESDP 1009 F. nucleatum P. gingivalis S. mutans T. denticola PF-C160 F. nucleatum AASGFTYCASNGVWHPY 1010 PF-C180 F. nucleatum TVEELDKAFTWGAAAALAIGVIAINVG 1011 P. gingivalis LAAGYCYNNNDVF S. mutans T. denticola PF-C181 P. gingivalis KMRAGQVVFIYKLILVLLFYVLQKLFD 1012 LKKGCF PF-C194 A. naeslundii NTNDLLQAFELMGLGMAGVFIVLGILYI 1013 F. nucleatum VAELLIKIFPVNN P. gingivalis S. mutans T. denticola PF-C259 F. nucleatum AEIQPHCLSVL 1014 S. mutans PF-C271 A. naeslundii FFPSYYSIIITYF 1015 F. nucleatum P. gingivalis S. mutans T. denticola PF-C273 A. naeslundii KNMLKRRMKQKRLFDEEDRLRVLSKY 1016 P. gingivalis TKSYY S. mutans T. denticola PF-C281 A. naeslundii KKEKLLTAIRLQHRAEIRGYFTIFFLFFRI 1017 F. nucleatum P. gingivalis S. mutans T. denticola PF-C285 A. naeslundii FTIIELKKQKIKHGENNKKTAHPLNEPF 1018 F. nucleatum CARA P. gingivalis S. mutans T. denticola PF-C290 A. naeslundii GNVHPESDFHNLIQFIKTFLYFTIFFKYF 1019 F. nucleatum L P. gingivalis S. mutans T. denticola PF-C291 A. naeslundii HPFLTGTGCPLFLIFRLFFVKAYFSFTVF 1020 F. nucleatum P. gingivalis S. mutans PF-S003 S. epidermidis ALALLKQDLLNFEGRGRIITSTYLQFNE 1021 M. luteus GCVP P. mirabilis E. coli P. aeruginosa C. albicans MRSA S. pneumoniae E. faecalis C. jeikeium C. jejuni M. smegmatis PF-S004 S. epidermidis VLLNIFRTLLEFFSPSNAPGAEDVPLPDT 1022 MRSA QA C. jeikeium PF-S007 S. epidermidis VVAGVVLLTALAVGSKRKEKKQIKEIQ 1023 MRSA RLLAATR PF-S015 S. epidermidis IENLERGARRPP 1024 MRSA C. jeikeium PF-S018 S. epidermidis GMPQIPRLRI 1025 M. luteus C. albicans MRSA E. faecalis C. jeikeium C. jejuni PF-S023 S. epidermidis MAEDERRALKRRTNRGRTRTRKRITV 1026 MRSA PF-S026 S. epidermidis TELKYNGEEYLLLTQRDILAVIEK 1027 MRSA C. jeikeium PF-S029 M. luteus TSDTQSQSPWLFDNADIVNIYPVQLMHS 1028 P. mirabilis SDND E. coli C. albicans C. jeikeium C. jejuni *Peptide binding was conducted in aqueous buffers that varied depending on peptide solubility. For example: Brain Heart Infusion (BHI) Media ; 1X Phosphate-buffered saline (PBS); 0.05% v/v Tween-20; 0.05% v/v Tween-80; 1% v/v Glycerol; 50 μM Guanidine hydrochloride; 0.05% v/v Acetic acid; 50 μM Urea; 1% v/v Polyethylene glycol 400 (PEG 400); 20 mM Sodium glutamate; 50 mM Piperazine-1,4-bis(2-ethanesulfonic acid)(PIPES); 50 mM Sodium acetate; 1% v/v Pluronic 17R4; 1% w/v Pluronic F108; 1% w/v Pluronic P123; 0.2% v/v Cetyl trimethylammonium bromide (CTAB); 0.8% v/v β-D-Octyl glucoside (BOG); 0.2% CTAB and 0.05% Tween-20; 0.2% CTAB and 0.05% Tween-80; 0.2% CTAB and 1% glycerol; and 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid ), 150 mM. sodium chloride, 1mM magnesium chloride and 0.1% CTAB. Preferably, binding was evaluated in 1x PBS. **Three-amino acid code: Dab: Diaminobutyric acid; Orn: Ornithine; cDOrn, cOrn: side-chain cyclical Ornithine; Abreviations: c(X . . . Y) indicates amino acids are cyclic, connected X to Y; DX indicates D-isoform amino acids.

In certain embodiments, the amino acid sequence of the targeting peptides comprises or consists of a single amino acid sequence, e.g., as listed above in Table 3. In certain embodiments the amino acid sequence of the targeting peptides comprises two copies, three copies, four copies, five copies six copies or more of one or more of the amino acid sequences listed in Table 3, and/or Table 10, and/or Table 12. Thus, compound targeting constructs are contemplated where the construct comprises multiple domains each having targeting activity. The targeting domains comprising such a construct can be the same or different. In certain embodiments the construct comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 different targeting domains each domain comprising a different targeting sequence.

Various targeting domains comprising such a construct can be joined directly to each other or two or more of such domains can be attached to each other via a linker. An illustrative, but non-limiting, list of suitable linkers is provided in Table 16. Thus, in certain embodiments, two or more targeting domains comprising a compound/multiple targeting construct are chemically conjugated together.

In certain embodiments the two or more targeting domains comprising the construct are joined by a peptide linker. Where all the targeting domains are attached directly to each other or are joined by peptide linkers, the entire construct can be provided as a single-chain peptide (fusion protein).

In various embodiments, the targeting peptides described herein comprise one or more of the amino acid sequences shown in Table 3, and/or Table 10, and/or Table 12 (and/or the retro, inverso, retroinverso, etc. forms of such sequences). In certain embodiments the peptides range in length up to about 100 amino acids in length, preferably up to about 80, about 70, about 60, or about 51 amino acids in length. In certain embodiments the peptides range in length from about 8 amino acids up to about 100 amino acids 80 amino acids, 60 amino acids or about 51 amino acids in length. In certain embodiments the peptides range in length from about 8 up to about 50, 40, 30, 20, 15, 15, 13, or 12 amino acids in length.

As shown in Tables 3, 10, and 12 the various amino acid sequences described herein target particular microorganisms. The range of activity of the peptides or compositions comprising such peptides can be increased by including amino acid sequences that target different microorganisms either as separate components and/or as multiple domains within a single construct.

In some embodiments greater specificity and/or avidity can be obtained by including multiple different amino acid sequences that target the same microorganism.

II. Antimicrobial Peptides.

A) Uses of Antimicrobial Peptides.

The antimicrobial peptides described herein also have a wide variety of uses. For example, the peptides can be formulated individually, in combination, in combination with other antimicrobial peptides, and/or in combination with various antibacterial agents to provide antimicrobial pharmaceuticals.

In various embodiments, the antimicrobial peptides described herein can be formulated individually, in combination, in combination with other antimicrobial peptides, and/or in combination with various antibiotic (e.g., antibacterial) agents in “home healthcare” formulations. Such formulations include, but are not limited to toothpaste, mouthwash, tooth whitening strips or solutions, contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasal application, wound dressings (e.g., bandages), and the like.

In various embodiments the antimicrobial peptides described herein can be formulated individually, in combination, in combination with other antimicrobial peptides, and/or in combination with various antibiotic (e.g., antibacterial) agents in various cleaning and/or sterilization formulations for use in agriculture, in fool preparation and transport, in the home, workplace, clinic, or hospital.

In certain embodiments the antimicrobial peptides described herein are attached to one or more targeting moieties to specifically and/or to preferentially deliver the peptide(s) to a target (e.g. a target microorganism, biofilm, bacterial film, particular tissue, etc.).

Other possible uses of the targeting and/or antimicrobial peptides disclosed herein include, but are not limited to biofilm dispersal, biofilm retention, biofilm formation, anti-biofilm formation, cell agglutination, induction of motility or change in motility type, chemoattractant or chemorepellent, extracellular signal for sporogenesis or other morphological change, induction or inhibition of virulence gene expression, utilized as extracellular scaffold, adhesin or binding site, induction or suppression of host immune response, induction or suppression of bacterial/fungal antimicrobial molecule production, quorum-sensing, induction of swarming behavior, apoptosis or necrosis inducing in eukaryotic cells, affecting control of or inducing the initiation of cell cycle in eukaryotes, in archaea or prokaryotes, induces autolysis or programmed cell death, inhibition of phage/virus attachment or replication, evasion of innate immunity, induction or inhibition of genetic transformation or transduction competence, induction or inhibition of pilus-mediated conjugation, induction or inhibition of mating behavior in bacteria and fungi, induction or inhibition of nodule formation or metabolic compartmentalization, metal, ion, or nutrient binding, acquisition or inhibition of metal, ion, or nutrient binding and acquisition, and the like.

In certain embodiments, compositions and methods are provided for decreasing the infectivity, morbidity, and rate of mortality associated with a variety of pathogens. The present invention also relates to methods and compositions for decontaminating areas, samples, solutions, and foodstuffs colonized or otherwise infected by pathogens and microorganisms. Certain embodiments of the present compositions are nontoxic and may be safely ingested by humans and other animals. Additionally, certain embodiments of the present invention are chemically stable and non-staining.

In some embodiments, the present invention provides compositions and methods suitable for treating animals, including humans, exposed to pathogens or the threat of pathogens. In some embodiments, the animal is contacted with effective amounts of the compositions prior to exposure to pathogenic organisms. In other embodiments, the animal or human is contacted with effective amounts of the compositions after exposure to pathogenic organisms. Thus, the present invention contemplates both the prevention and treatment of microbiological and other infections.

In certain embodiments compositions and methods are provided for decontaminating solutions and surfaces, including organic and inorganic samples that are exposed to pathogens or suspected of containing pathogens. In still other embodiments of the present invention, the compositions are used as additives to prevent the growth of harmful or undesired microorganisms in biological and environmental samples.

These applications of the peptides described herein are intended to be illustrative and not limiting. Using the teaching provided herein, other uses will be recognized by one of skill in the art.

B Illustrative Novel Antimicrobial Peptides.

Antimicrobial peptides (also called host defense peptides) are an evolutionarily conserved component of the innate immune response and are found among all classes of life. Unmodified, these peptides are potent, broad spectrum antibiotics which demonstrate potential as novel therapeutic agents. Antimicrobial peptides have been demonstrated to kill Gram-negative and Gram-positive bacteria (including strains that are resistant to conventional antibiotics), mycobacteria (including Mycobacterium tuberculosis), enveloped viruses, and fungi.

Naturally-occurring antimicrobial peptides are typically short peptides, generally between 12 and 50 amino acids. These peptides often include two or more positively charged residues provided by arginine, lysine or, in acidic environments, histidine, and frequently a large proportion (generally >50%) of hydrophobic residues (see, e.g., Papagianni et al. (2003) Biotechnol Adv 21: 465; Sitaram and Nagaraj (2002) Curr Pharm Des 8: 727; Dun et al. (2006) Biochim. Biophys. Acta 1758: 1408-1425).

Frequently the secondary structures of these molecules follow 4 themes, including i) α-helical, ii) β-stranded due to the presence of 2 or more disulfide bonds, iii) β-hairpin or loop due to the presence of a single disulfide bond and/or cyclization of the peptide chain, and iv) extended. Many of these peptides are unstructured in free solution, and fold into their final configuration upon partitioning into biological membranes. The ability to associate with membranes is a definitive feature of antimicrobial peptides although membrane permeabilisation is not necessary. These peptides have a variety of antimicrobial activities ranging from membrane permeabilization to action on a range of cytoplasmic targets.

The modes of action by which antimicrobial peptides kill bacteria is varied and includes, but is not limited to disrupting membranes, interfering with metabolism, and targeting cytoplasmic components. In many cases the exact mechanism of killing is not known.

In certain embodiments the antimicrobial peptides include peptides comprising or consisting of one or more of the amino acid sequences shown in Tables 4 (SEQ ID NOs:1029-1078), and/or Table 5 (SEQ ID NOs:1079-1566). In various embodiments the peptides include peptides comprising or consisting of the retro, inverso, retro-inverso, and/or beta form of one or more of the amino acid sequences shown in Tables 4 (SEQ ID NOs:1029-1078), and/or Table 5 (SEQ ID NOs:1079-1566). The peptides can comprise all “L” amino acids, all “D” amino acids, or combinations of “L” and “D” amino acids. Also contemplated are circular permutations of these sequences as well as peptides comprising or consisting of the retro, inverso, retro-inverso, and/or beta form of such circular permutations.

It will also be recognized, that in certain embodiments, any peptide or compound AMP described herein can be circularized.

In various embodiments the peptides can optionally bear one or more protecting groups, e.g., and the amino and/or carboxyl termini, and/or on side chains.

Also contemplated are peptides comprising one, two, three four, or five conservative substitutions of these amino acid sequences.

TABLE 4 Novel antimicrobial peptides, target micro- organisms and MIC values. SEQ Organism MIC ID ID (μM) Structure/sequence NO K-1 S. mutans, 25 GLGRVIGRLIKQIIWRR 1029 K-2 S. mutans, 12.5 VYRKRKSILKIYAKLKGW 1030 H K-7 S. mutans, 12.5 NYRLVNAIFSKIFKKKFI 1031 KF K-8 S. mutans, 4 KILKFLFKKVF 1032 K-9 S. mutans, 4 FIRKFLKKWLL 1033 K-10 S. mutans, 4 KLFKFLRKHLL 1034 K-11 S. mutans, 4 KILKFLFKQVF 1035 K-12 S. mutans, 8 KILKKLFKFVF 1036 K-13 S. mutans, 16 GILKKLFTKVF 1037 K-14 S. mutans, 8 LRKFLHKLF 1038 K-15 S. mutans, 4 LRKNLRWLF 1039 K-16 S. mutans, 8 FIRKFLQKLHL 1040 P. aeruginosa, 12.5 MRSA, 25 K-17 S. mutans, 8 FTRKFLKFLHL 1041 K-18 S. mutans, 16 KKFKKFKVLKIL 1042 K-19 S. mutans, 16 LLKLLKLKKLKF 1043 K-20 S. mutans, 8 FLKFLKKFFKKLKY 1044 K-21 S. mutans, 8 GWLKMFKKIIGKFGKF 1045 K-22 S. mutans, 8 GIFKKFVKILYKVQKL 1046 1T-88 GRLVLEITADEVKALGEA 1047 LANAKI PF-531 A. baumannii, 25 YIQFHLNQQPRPKVKKIK 1048 P. aeruginosa, 50 IFL-NH2 T. rubrum, 50 A. niger, 25 B. subtilis, 25 C. difficile, 12.5 C. jeikeium, 6.25 S. epidermidis, 50 S. mutans, 12.5 PF-527 P. aeruginosa, 50 GSVIKKRRKRMAKKKHRK 1049 T. rubrum, 25 LLKKTRIQRRRAGK A. niger, 50 B. subtilis, 12.5 C. jeikeium, 6.25 MRSA, 50 S. epidermidis, 25 PF-672 C. albicans, 1.56 MRFGSLALVAYDSAIKHS 1050 T. rubrum, 0.78 WPRPSSVRRLRM A. niger, 3 B. subtilis, 0.78 E. faecalis, 3.13 MRSA, 1.56 S. epidermidis, 0.39 PF-606 E. coli, 50 FESKILNASKELDKEKKV 1051 MRSA, 50 NTALSFNSHQDFAKAYQN S. epidermidis, 50 GKI S. mutans, 50 S. pneumoniae, 50 PF-547 T. rubrum, 25 WSRVPGHSDTGWKVWHR 1052 B. subtilis, 25 W-NH2 S. mutans, 12.5 PF-006 A. baumannii, 50 MGIIAGIIKFIKGLIEKF 1053 B. subtilis, 25 TGK MRSA, 50 PF-545 A. niger, 50 RESKLIAMADMIRRRI- 1054 B. subtilis, 25 NH2 MRSA, 50 PF-278 C. albicans, 50 LSLATFAKIFMTRSNWSL 1055 T. rubrum, 50 KRFNRL S. epidermidis, 50 PF-283 T. rubrum, 50 MIRIRSPTKKKLNRNSIS 1056 B. subtilis, 50 DWKSNTSGRFFY S. epidermidis, 50 PF-307 C. albicans, 50 MKRRRCNWCGKLFYLEEK 1057 T. rubrum, 50 SKEAYCCKECRKKAKKVK B. subtilis, 50 K PF-168 T. rubrum, 50 VLPFPAIPLSRRRACVAA 1058 A. niger, 50 PRPRSRQRAS MRSA, 50 PF-538 A. baumannii, 25 KNKKQTDILEKVKEILDK 1059 C. difficile, 25 KKKTKSVGQKLY PF-448 A. niger, 25 SLQSQLGPCLHDQRH 1060 S. pneumoniae, 50 PF-583 MRSA, 50 KFQGEFTNIGQSYIVSAS 1061 S. epidermidis, 50 HMSTSLNTGK PF-600 E. coli, 50 TKKIELKRFVDAFVKKSY 1062 S. pneumoniae, 50 ENYILERELKKLIKAINE ELPTK PF-525 A. niger, 50 KFSDQIDKGQDALKDKLG 1063 S. pneumoniae, 50 DL PF-529 A. niger, 50 LSEMERRRLRKRA-NH2 1064 S. pneumoniae, 50 PF-148 A. niger, 50 RRGCTERLRRMARRNAWD 1065 B. subtilis, 50 LYAEHFY PF-530 A. baumannii, 25 SKFKVLRKIIIKEYKGEL 1066 MLSIQKQR PF-522 C. difficile, 25 FELVDWLETNLGKILKSK 1067 SA-NH2 PF-497 B. subtilis, 50 LVLRICTDLFTFIKWTIK 1068 QRKS PF-499 B. subtilis, 50 VYSFLYVLVIVRKLLSMK 1069 KRIERL PF-322 B. subtilis, 50 GIVLIGLKLIPLLANVLR 1070 PF-511 S. pneumoniae, 50 VMQSLYVKPPLILVTKLA 1071 QQN PF-512 S. pneumoniae, 50 SFMPEIQKNTIPTQMK 1072 PF-520 S. pneumoniae, 50 LGLTAGVAYAAQPTNQPT 1073 NQPTNQPTNQPTNQPTNQ PRW-NH2 PF-521 S. pneumoniae, 50 CGKLLEQKNFFLKTR 1074 PF-523 S. pneumoniae, 50 ASKQASKQASKQASKQAS 1075 KQASRSLKNHLL PF-524 S. pneumoniae, 50 PDAPRTCYHKPILAALSR 1076 IVVTDR PF-209 MRSA, 50 NYAVVSHT 1077 PF-437 S. pneumoniae, 50 FQKPFTGEEVEDFQDDDE 1078 IPTII Where protecting groups are shown (e.g., —NH₂) they are optional. Conversely any peptide shown without protecting groups can bear one or more such groups.

In certain embodiments peptides that induce alterations in phenotype or other biological activities can also be used as antimicrobial effector moieties. Illustrative alternative peptides are shown in Table 5.

TABLE 5 Illustrative list of novel morphology, biofilm and growth disrupting peptides. ID Organism, effect Structure/sequence SEQ ID NO G-1 S. mutans: Ca2+ DSSQSDSDSDSNSSNTNSNSSITNG 1079 binding G-2 S. mutans: biofilm LPGTLHIQAEFPVQLEAGSLIQIFD 1080 structure G-4 S. mutans: EIPIQLANDLANYYDISLDSIFFW 1081 Biofilm structure G-5 M. xanthus: RDMTVAGKRPNFLIITTDEE 1082 Altered cell morphology G-6 M. xanthus: NTSIVCAVTFAPIKEVPLLWRAGLTLRS 1083 Altered cell RQS morphology G-7 M. xanthus: QAKVEREVERDLVYTLRRLCDPSGSER 1084 Altered cell TK morphology G-8 S. mutans: PRMIDIISFHGCHGDHQVWTDPQATAL 1085 Altered biofilm PR structure PF-001 S. epidermidis (C) MNNWIIVAQLSVTVINEIIDIMKEKQKG 1086 M. luteus (C) GK MRSA (R) C. jeikeium (D) PF-002 B. subtilis (R) NDDAQ 1087 S. pneumoniae (H) PF-003 S. epidermidis (D) MNNWIKVAQISVTVINEVIDIMKEKQN 1088 M. luteus (A) GGK MRSA (R) C. jeikeium (A) PF-004 S. epidermidis (A) ARLSKAIIIAVIVVYHLDVRGLF 1089 M. luteus (A) MRSA (R) C. jeikeium (A) PF-005 B. subtilis (C) MESIFKIKLMNGICRSENMNMKKKNK 1090 S. pneumoniae (H) GEKI PF-006 S. epidermidis (D) MGIIAGIIKFIKGLIEKFTGK 1091 M. luteus (A) B. subtilis (I) MRSA (I) S. pneumoniae (R) C. jejuni (D) PF-007 S. epidermidis (A) MGIIAGIIKVIKSLIEQFTGK 1092 M. luteus (A) E. coli (A) MRSA (R) E. faecalis (A) PF-008 B. subtilis (D) MIEIGSIAYLNGGSKKYNHILNQENR 1093 C. jejuni (R) PF-009 S. epidermidis (S) SKKYNHILNQENR 1094 PF-010 S. epidermidis (S) MDIDVNKLLQAFVYFKSFEKLRHNNS 1095 M. luteus (A) MRSA (R) C. jeikeium (A) PF-011 MRSA (R) MFCYYKQHKGDNFSIEEVKNIIADNEM 1096 C. jeikeium (C) KVN PF-012 S. epidermidis (S) WRGPNTEAGGKSANNIVQVGGAPT 1097 M. luteus (C) MRSA (R) C. jeikeium (A) PF-013 S. epidermidis (C) LIQKGLNQTFIVVIRLNNFIKKS 1098 M. luteus (D) MRSA (R) C. jeikeium (D) PF-015 MRSA (W) SIDKRNLYNLKYYE 1099 PF-017 MRSA (M) ESIIE 1100 PF-019 MRSA (M) NDTNK 1101 PF-020 S. mutans (F) MKIILLLFLIFGFIVVVTLKSEHQLTLFSI 1102 S. epidermidis (C) M. luteus (C) MRSA (C) S. pneumoniae (D) PF-021 S. epidermidis (A) FSLNFSKQKYVTVN 1103 M. luteus (A) MRSA (R) C. jeikeium (R) PF-022 S. epidermidis (D) MINELKNKNSGIMNNYVVTKESKL 1104 M. luteus (A) MRSA (R) C. jeikeium (A) PF-023 MRSA (S) MTKNTIISLENEKTQINDSENESSDLRK 1105 AK PF-024 S. epidermidis (D) DLRKAK 1106 MRSA (M) PF-025 S. epidermidis (S) LLIIFRLWLELKWKNKK 1107 M. luteus (A) MRSA (R) C. jeikeium (A) PF-026 MRSA (M) SIHFIN 1108 PF-027 S. epidermidis (D) HNARKYLEFISQKIDGDKLTKEDSL 1109 MRSA (M) PF-028 S. epidermidis (M) ALDCSEQSVILWYETILDKIVGVIK 1110 MRSA (R) C. jeikeium (M) PF-029 MRSA (M) NSTNE 1111 PF-030 S. epidermidis (D) MTCHQAPTTTHQSNMA 1112 M. luteus (C) MRSA (R) C. jeikeium (C) PF-031 MRSA (M) MPHHSTTSSRIVVPAHQSNMASTPNLSI 1113 TP PF-032 S. epidermidis (S) RIVVPAHQSNMASTPNLSITP 1114 C. jeikeium (C) PF-033 S. epidermidis (M) MFIFKTTSKSHFHNNVKSLECIKIPINK 1115 B. subtilis (C) NR MRSA (M) S. pneumoniae (R) C. jeikeium (D) C. jejuni (R) PF-034 S. epidermidis (A) EPKKKHFPKMESASSEP 1116 PF-035 MRSA (M) SFYESY 1117 PF-036 S. epidermidis (S) ILNRLSRIVSNEVTSLIYSLK 1118 M. luteus (A) MRSA (R) C. jeikeium (A) PF-037 S. epidermidis (D) MTKKRRYDTTEFGLAHSMTAKITLHQ 1119 M. luteus (C) ALYK MRSA (R) C. jeikeium (D) PF-040 S. mutans (F) MIHLTKQNTMEALHFIKQFYDMFFILN 1120 S. epidermidis (D) FNV M. luteus (D) B. subtilis (D) P. mirabilis (C) E. coli (C) MRSA (D) S. pneumoniae (D) C. jeikeium (D) C. jejuni (D) PF-041 S. epidermidis (R) ELLVILPGFI 1121 MRSA (M) PF-042 S. epidermidis (D) LLLSYFRYTGALLQSLF 1122 M. luteus (C) MRSA (R) C. jeikeium (S) PF-043 S. epidermidis (D) MIKNETAYQMNELLVIRSAYAK 1123 M. luteus (C) MRSA (R) C. jeikeium (A) PF-045 MRSA (S) LDINDYRSTY 1124 PF-046 S. epidermidis (C) LDFYLTKHLTLML 1125 MRSA (R) C. jeikeium (R) PF-048 S. epidermidis (D) LYFAFKKYQERVNQAPNIEY 1126 MRSA (W) C. jeikeium (S) PF-049 MRSA (S) AYYLKRREEKGK 1127 PF-051 S. mutans (D) RFFNFEIKKSTKVDYVFAHVDLSDV 1128 S. epidermidis (D) M. luteus (C) MRSA (D) S. pneumoniae (D) PF-052 S. epidermidis (S) QELINEAVNLLVKSK 1129 M. luteus (A) MRSA (R) C. jeikeium (D) PF-053 S. epidermidis (C) KLFGQWGPELGSIYILPALIGSIILIAIVT 1130 M. luteus (D) LILRAMRK B. subtilis (H) E. coli (A) P. aeruginosa (A) C. albicans (A) MRSA (D) S. pneumoniae (S) E. faecalis (A) C. jeikeium (D) C. jejuni (D) PF-056 S. epidermidis (D) AEQLFGKQKQRGVDLFLNRLTIILSILF 1131 M. luteus (D) FVLMICISYLGM B. subtilis (C) C. albicans (B) MRSA (M) S. pneumoniae (D) C. jeikeium (S) C. jejuni (D) PF-057 S. epidermidis (D) TMIVISIPRFEEYMKARHKKWM 1132 M. luteus (C) E. coli (M) C. albicans (A) MRSA (M) S. pneumoniae (R) E. faecalis (A) C. jeikeium (A) C. jejuni (D) PF-058 MRSA (M) FADQSQDNA 1133 PF-059 C. jejuni (C) TITLKAGIERALHEEVPGVIEVEQVF 1134 PF-061 S. epidermidis (R) GYNSYKAVQDVKTHSEEQRVTAKK 1135 B. subtilis (R) S. pneumoniae (R) C. jejuni (R) PF-063 S. epidermidis (R) IAAIIVLVLFQKGLLQIFNWILIQLQ 1136 M. luteus (R) B. subtilis (C) P. aeruginosa (A) MRSA (M) S. pneumoniae (D) C. jeikeium (D) C. jejuni (D) PF-064 S. epidermidis (D) DYYGKE 1137 MRSA (M) PF-065 S. epidermidis (D) LEKNTRDNYFIHAIDRIYINTSKGLFPES 1138 MRSA (R) ELVAWG C. jeikeium (A) PF-066 MRSA (S) IKGTVKAVDETTVVITVNGHGTELTFE 1139 KPAIKQVDPS PF-067 S. epidermidis (D) DLIVKVHICFVVKTASGYCYLNKREAQ 1140 M. luteus (R) AAI B. subtilis (C) P. aeruginosa (A) MRSA (M) S. pneumoniae (D) C. jeikeium (D) C. jejuni (D) PF-068 S. epidermidis (M) SHLINNFGLSVINPSTPICLNFSPVFNLL 1141 M. luteus (D) TVYGITCN B. subtilis (A) E. coli (A) MRSA (M) S. pneumoniae (D) E. faecalis (A) C. jeikeium (R) C. jejuni (D) PF-069 B. subtilis (D) FDPVPLKKDKSASKHSHKHNH 1142 C. jejuni (R) PF-070 B. subtilis (D) SMVKSEIVDLLNGEDNDD 1143 PF-071 S. epidermidis (R) HCVIGNVVDIANLLKRRAVYRDIADVI 1144 M. luteus (R) KMR B. subtilis (D) C. albicans (B) MRSA (C) S. pneumoniae (A) C. jejuni (A) PF-073 S. epidermidis (R) CPSVTMDACALLQKFDFCNNISHFRHF 1145 M. luteus (R) FAIKQPIER MRSA (M) S. pneumoniae (D) C. jeikeium (D) C. jejuni (D) PF-074 S. epidermidis (D) RDIHPIYFMTKD 1146 MRSA (M) PF-075 S. epidermidis (D) FVNSLIMKDLSDNDMRFKYEYYNREK 1147 M. luteus (A) DT MRSA (R) C. jeikeium (D) PF-076 S. epidermidis (S) LYQYELLSKEEYLKCTLIINQRRNEQK 1148 M. luteus (A) MRSA (R) C. jeikeium (A) PF-099 S. epidermidis (D) EIIAYLEGRFANA 1149 C. jeikeium (C) PF-123 S. epidermidis (M) TTRPQVAEDRQLDDALKETFPASDPISP 1150 PF-124 S. epidermidis (C) MADGQIAAIAKLHGVPVATRNIRHFQS 1151 C. jeikeium (R) FGVELINPWSG PF-125 S. epidermidis (D) YVVGALVILAVAGLIYSMLRKA 1152 M. luteus (C) PF-127 S. epidermidis (M) MLRYLSLFAVGLATGYAWGWIDGLA 1153 M. luteus (A) ASLAV C. jeikeium (A) PF-128 S. epidermidis (D) GIKVVAARFEEIQFSENFDSIILA 1154 P. aeruginosa (C) PF-129 S. epidermidis (M) MKLLARDPWVCAWNDIW 1155 C. jeikeium (R) PF-133 C. jeikeium (R) GDPTAGQKPVECP 1156 PF-135 C. jeikeium (R) PPARPARIPQTPTLHGASLFRQRS 1157 PF-137 S. epidermidis (D) VLGKGHDLLDVGKTALKSRVFAWLG 1158 M. luteus (D) GS C. jeikeium (A) PF-139 S. epidermidis (M) ALSKPAIQARTLCRRQDPP 1159 M. luteus (C) C. jeikeium (R) PF-140 S. epidermidis (D) FHRRVIRASEWALTTRSFSTPLRSAAR 1160 M. luteus (R) P. aeruginosa (A) C. albicans (B) MRSA (M) S. pneumoniae (D) C. jeikeium (D) C. jejuni (D) PF-143 P. aeruginosa (C) LSPRPIIVSRRSRADNNNDWSR 1161 PF-144 S. pneumoniae (H) RSGQPVGRPSRRAWLR 1162 PF-145 S. epidermidis (D) GIVLTGRAGLVSGACSMALGVGLG 1163 M. luteus (A) B. subtilis (C) MRSA (M) S. pneumoniae (R) C. jeikeium (R) C. jejuni (R) PF-148 S. epidermidis (D) RRGCTERLRRMARRNAWDLYAEHFY 1164 M. luteus (A) B. subtilis (I) C. albicans (B) MRSA (C) S. pneumoniae (R) C. jeikeium (H) C. jejuni (H) PF-149 MRSA (H) GKVSVLTRVPRSLGGAPANQ 1165 PF-153 S. epidermidis (M) GILARADCSQIA 1166 C. jeikeium (C) PF-156 MRSA (H) LITAEQPATAPIAGK 1167 PF-157 S. epidermidis (M) HTAVVWLAGVSGCVALSHCEPA 1168 PF-164 C. jeikeium (R) EEVSRALAGIGLGLGCRIG 1169 PF-168 P. aeruginosa (H) VLPFPAIPLSRRRACVAAPRPRSRQRAS 1170 MRSA (I) PF-171 S. epidermidis (R) TQVTLCRTW 1171 M. luteus (R) B. subtilis (D) MRSA (M) S. pneumoniae (D) C. jejuni (R) PF-173 S. epidermidis (A) AGRTAIVQGGG 1172 C. jeikeium (D) PF-175 M. luteus (S) RRRPAGQRPEKASQAMIAA 1173 B. subtilis (D) C. albicans (B) S. pneumoniae (A) C. jejuni (M) PF-176 S. epidermidis (C) RLTSNQFLTRITPFVFAQH 1174 M. luteus (C) C. jeikeium (D) PF-178 S. epidermidis (D) EVYSSPTNNVAITVQNN 1175 E. coli (C) MRSA (M) S. pneumoniae (D) PF-180 S. epidermidis (C) SGLGDLGFSSEAK 1176 PF-186 S. epidermidis (C) DADKNLSLERDRFAWRVAAP 1177 C. jeikeium (A) PF-188 C. jeikeium (H) ARTFAGRLGTRYFGGLMRSTKA 1178 PF-190 S. epidermidis (C) HFILRKPLLFMIHSLKTGPLDRF 1179 C. jeikeium (R) PF-191 S. epidermidis (A) QFCNFAWLFLASNNAQVSALA 1180 MRSA (H) C. jeikeium (R) PF-192 S. epidermidis (D) VEEDEAPPPHY 1181 PF-196 S. epidermidis (C) TTARYIRRQCHTSITPLSQG 1182 C. jeikeium (R) PF-199 S. epidermidis (C) FPAFSFGAIAGSVSVAR 1183 M. luteus (A) C. jeikeium (R) PF-203 S. epidermidis (A) SWKCHHLAI 1184 C. jeikeium (R) PF-204 S. epidermidis (C) ALQKQDMNLPSVKNQLVFLKSTG 1185 M. luteus (C) P. aeruginosa (H) C. jeikeium (D) PF-208 S. epidermidis (D) DAYHCHLVRSPDAHDLSMRIGFV 1186 C. jeikeium (A) PF-209 S. epidermidis (C) NYAVVSHT 1187 P. aeruginosa (H) MRSA (I) PF-212 M. luteus (M) NDSKASN 1188 PF-215 M. luteus (T) ELKITNYNVNTVLYRYYKWGNDLCE 1189 PF-220 S. pneumoniae (H) VDPADDGTRHIRPEDGDPIEIDE 1190 PF-224 M. luteus (T) DYFYITLSQKNTF 1191 PF-226 S. epidermidis (C) LMFFSENMDKRDTLSGKFRYFAGSKVI 1192 M. luteus (T) KLMNWLSENGK PF-233 S. epidermidis (C) DANAMARTTIAIVYILALIALTISYSL 1193 PF-234 M. luteus (T) RTPYILRS 1194 PF-235 M. luteus (T) GIPFSKPHKRQVNYMKSDVLAYIEQNK 1195 MAHTA PF-249 M. luteus (R) INSRYKISF 1196 PF-250 M. luteus (T) SEDIFGRLANEKANGLEELRKIRLKQ 1197 PF-255 M. luteus (M) DHKINESQHNPFRSDSNKQNVDFF 1198 PF-257 M. luteus (R) VWENRKKYLENEIERHNVFLKLGQEVI 1199 KGLNALASRGR PF-264 M. luteus (H) MQSLSNRQSLIASYILMGIFLSFGYPPA 1200 SLSKFFCRLSHL PF-270 M. luteus (H) MYLTPYAWIAVGSIFAFSVTTIKIGDQN 1201 DEKQKSHKNDVHKR PF-271 M. luteus (T) AAQPQTTSP 1202 PF-273 S. epidermidis (C) LVGALLIFVALIYMVLKGNADKN 1203 PF-274 M. luteus (M) SIQEAEKIIKNDPFYIHDVADYDFMWF 1204 EPSKSLEEIKEFV PF-276 M. luteus (M) LDLALSTNSLNLEGFSF 1205 PF-278 S. epidermidis (I) LSLATFAKIFMTRSNWSLKRFNRL 1206 M. luteus (R) C. albicans (B) PF-283 S. epidermidis (H) MIRIRSPTKKKLNRNSISDWKSNTSGRF 1207 B. subtilis (H) FY PF-289 B. subtilis (C) MGRHLWNPSYFVATVSENTEEQIRKY 1208 RKNK PF-290 S. epidermidis (C) MVHDMTNGTLIIVKH 1209 PF-292 S. epidermidis (C) SFVSTTVRLIFEESKRYKF 1210 B. subtilis (C) PF-293 S. epidermidis (C) YDPLK 1211 PF-294 S. epidermidis (C) DFLVNFLWFKGELNWGKKRYK 1212 PF-296 S. epidermidis (C) GAFGMPSIKTNTICGEKGKFISACDAW 1213 B. subtilis (C) LSNLK PF-297 S. epidermidis (C) ISKGIDDIVYVINKILSIGNIFKIIKRK 1214 B. subtilis (C) PF-301 S. epidermidis (C) GIVLIGLKLIPLLANVLN 1215 B. subtilis (C) PF-303 B. subtilis (C) EYPWSWISEPWPWDKSFYK 1216 PF-305 B. subtilis (C) MREWICPSCNETHDRDINASINILKEGL 1217 RLITIQNK PF-306 B. subtilis (C) GCILPHKKDNYNYIMSKFQDLVKITSK 1218 K PF-307 S. epidermidis (T) MKRRRCNWCGKLFYLEEKSKEAYCC 1219 B. subtilis (H) KECRKKAKKVKK C. albicans (B) PF-310 S. epidermidis (C) GVALIGTILVPLLSGLFG 1220 PF-313 S. epidermidis (C) YITSHKNARAIIKKFERDEILEEVITHYL 1221 NRK PF-318 S. epidermidis (C) MGRHLWNPSYFVATVSENTEEQIRKYI 1222 B. subtilis (C) NNQKKQVK PF-319 S. epidermidis (C) SIGSMIGMYSFRHKTKHIKFTFGIPFILF 1223 B. subtilis (C) LQFLLVYFYILK PF-322 S. epidermidis (C) GIVLIGLKLIPLLANVLR 1224 B. subtilis (H) PF-335 S. epidermidis (C) AAYPIEDWSDWYEDFFIMLSNI 1225 B. subtilis (C) PF-339 S. epidermidis (C) KKIDILINKYMYLSK 1226 B. subtilis (C) PF-342 S. epidermidis (C) AFSGVYKTLIVYTRRK 1227 B. subtilis (C) PF-344 E. coli (A) DERLPEAKAIRNFNGSVMVLGR 1228 PF-347 S. epidermidis (C) GIFTGVTVVVSLKHC 1229 E. coli (C) MRSA (C) E. faecalis (C) PF-349 S. epidermidis (C) MPKSCHVPVLCDFFFLVIIKFLALFKTI 1230 E. coli (C) QS MRSA (C) E. faecalis (C) PF-350 S. epidermidis (C) LAVILRAIVY 1231 E. coli (C) MRSA (C) PF-354 MRSA (H) FTFSKCRASNGRGFGTLWL 1232 PF-355 S. epidermidis (C) WIAIGLLLYFSLKNQ 1233 E. coli (C) P. aeruginosa (A) MRSA (A) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-356 S. epidermidis (S) VSIKIGAIVIGMIGLMELLTE 1234 P. aeruginosa (A) MRSA (C) S. pneumoniae (R) E. faecalis (R) C. jejuni (D) PF-357 S. epidermidis (M) MLTIIIGFIFWTMTLMLGYLIGEREGRK 1235 M. luteus (C) HE MRSA (M) S. pneumoniae (M) PF-360 S. epidermidis (S) MEQKVKVIFVPRSKPDNQLKTFVSAVL 1236 E. coli (C) FKA MRSA (H) PF-362 E. coli (C) NIERILKEKVWMIRCVE 1237 MRSA (C) PF-363 S. epidermidis (S) SMLSVTVMCLMHASVAANQAMEKKV 1238 E. coli (C) MRSA (H) S. pneumoniae (R) E. faecalis (D) C. jejuni (D) PF-366 S. epidermidis (R) ALCSVIKAIELGIINVHLQ 1239 E. coli (C) P. aeruginosa (A) MRSA (D) S. pneumoniae (C) E. faecalis (C) C. jejuni (D) PF-369 S. epidermidis (S) MSEAVNLLRGARYSQRYAKNQVPYEV 1240 E. coli (R) IIEK MRSA (H) E. faecalis (C) PF-370 S. epidermidis (C) VIFLHKESGNLKEIFY 1241 E. coli (R) MRSA (C) PF-373 S. epidermidis (M) HFYLLFER 1242 MRSA (M) PF-374 S. epidermidis (C) HLFFVKGMFILCQKNQINDE 1243 E. coli (C) MRSA (M) E. faecalis (C) PF-375 S. epidermidis (C) MDSAKAQTMRTDWLAVSCLVASAYL 1244 E. coli (C) RSMLA MRSA (C) E. faecalis (C) PF-376 S. epidermidis (C) MTVFEALMLAIAFATLIVKISNKNDKK 1245 E. coli (C) MRSA (C) E. faecalis (C) PF-378 S. epidermidis (M) ESAKSNLNFLMQEEWALFLLL 1246 MRSA (M) PF-379 S. epidermidis (C) VFVVLFIIYLASKLLTKLFPIKK 1247 E. coli (C) MRSA (C) E. faecalis (C) PF-380 S. epidermidis (C) KKIIPLITLFVVTLVG 1248 E. coli (C) P. aeruginosa (A) MRSA (D) S. pneumoniae (D) E. faecalis (C) C. jejuni (D) PF-381 S. epidermidis (C) QGANPCQQVGFTVNDPDCRLAKTV 1249 E. coli (R) MRSA (C) E. faecalis (C) PF-382 MRSA (M) KYKCSWCKRVYTLRKDHKTAR 1250 PF-383 S. epidermidis (C) WSEIEINTKQSN 1251 E. coli (R) PF-385 E. coli (A) MIKKSILKIKYYVPVLISLTLILSA 1252 PF-386 S. epidermidis (C) FTLTLITTIVAILNYKDKKK 1253 E. coli (C) MRSA (C) E. faecalis (C) PF-387 S. epidermidis (C) GAVGIAFFAGNMKQDKRIADRQNKKS 1254 E. coli (M) EKK MRSA (C) E. faecalis (C) PF-389 S. epidermidis (R) GLQFKEIAEEFHITTTALQQWHKDNGY 1255 MRSA (C) PIYNKNNRK S. pneumoniae (D) E. faecalis (R) C. jejuni (R) PF-390 S. epidermidis (D) VVAYVITQVGAIRF 1256 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-392 MRSA (S) DPAGCNDIVRKYCK 1257 E. faecalis (A) C. jejuni (A) PF-393 S. epidermidis (R) DLVQSILSEFKKSG 1258 MRSA (C) S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-394 MRSA (C) VLKEECYQKN 1259 E. faecalis (A) PF-395 S. epidermidis (C) YCVPLGNMGNMNNKIW 1260 E. coli (R) MRSA (C) PF-396 S. epidermidis (S) LIYTILASLGVLTVLQAILGREPKAVKA 1261 E. coli (C) MRSA (C) E. faecalis (C) PF-397 S. epidermidis (C) VEDLMEDLNA 1262 PF-398 S. epidermidis (C) ILVVLAGILLVVLSYVGISKFKMNC 1263 E. coli (C) MRSA (C) E. faecalis (C) PF-399 S. epidermidis (C) FPIISALLGAIICIAIYSFIVNRKA 1264 E. coli (C) MRSA (C) E. faecalis (C) PF-401 S. epidermidis (C) YWLSRVTTGHSFAFEKPVPLSLTIK 1265 E. coli (R) MRSA (C) E. faecalis (C) PF-403 S. epidermidis (M) LLSTEQLLKYYDGETFDGFQLPSNE 1266 E. coli (R) MRSA (M) PF-404 S. epidermidis (M) VLYFQATVV 1267 MRSA (M) PF-405 MRSA (M) LVRIEVDDLEEWYERNFI 1268 PF-406 S. epidermidis (C) YLEMNADYLSNMDIFDELWEKYLENN 1269 MRSA (M) K PF-407 S. epidermidis (M) KPKNKKEKTVISYEKLLSMY 1270 MRSA (C) S. pneumoniae (R) E. faecalis (R) PF-408 S. epidermidis (M) YCVPLGNMGNMNNKIW 1271 MRSA (M) PF-410 S. epidermidis (C) FALELIALCRNLFIVYFP 1272 E. coli (S) MRSA (M) E. faecalis (C) PF-411 S. epidermidis (C) WVAVAILLNIALQTQLT 1273 E. coli (C) P. aeruginosa (A) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-413 S. epidermidis (C) TFAGSIKIGVPDLVHVTFNCKR 1274 E. coli (S) MRSA (C) PF-414 S. pneumoniae (H) LLNKKLE 1275 PF-415 S. pneumoniae (D) MIDVTIGQKSKTGAFNASYSICFSGENF 1276 SF PF-416 S. pneumoniae (H) SKAGLYGKIERSDKRE 1277 PF-417 S. epidermidis (M) DSYFRS 1278 MRSA (M) S. pneumoniae (M) PF-418 S. epidermidis (M) FFLVHFYIRKRKGKVSIFLNYF 1279 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-419 S. pneumoniae (H) VVTGKVGSLPQIK 1280 PF-421 S. pneumoniae (H) KHCFEITDKTDVV 1281 PF-422 S. epidermidis (R) MSRKKYENDEKSQKKLKIGRKSDVFY 1282 MRSA (C) GIID S. pneumoniae (C) E. faecalis (R) C. jejuni (R) PF-423 S. pneumoniae (H) AGKKERLLSFREQFLNKNKKK 1283 PF-424 S. pneumoniae (H) IAAFVTSRAFSDTVSPI 1284 PF-425 S. epidermidis (D) MMELVLKTIIGPIVVGVVLRIVDKWLN 1285 E. coli (C) KDK P. aeruginosa (A) C. albicans (A) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-426 S. epidermidis (D) MLQKYTQMISVTKCIITKNKKTQENVD 1286 E. coli (C) AYN C. albicans (A) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-427 E. coli (C) YVLEYHGLRATQDVDAFMAL 1287 MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-428 S. pneumoniae (H) ENEESIF 1288 PF-429 S. epidermidis (C) AATLICVGSGIMSSL 1289 MRSA (C) S. pneumoniae (M) E. faecalis (C) PF-430 S. epidermidis (M) AVVCGYLAYTATS 1290 MRSA (M) S. pneumoniae (M) PF-431 S. epidermidis (M) VAYAAICWW 1291 MRSA (C) S. pneumoniae (R) E. faecalis (R) C. jejuni (R) PF-432 S. epidermidis (M) FNGDSEFFLCIAF 1292 E. coli (R) P. aeruginosa (A) MRSA (M) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-433 S. pneumoniae (H) MRKEFHNVLSSGQLLADKRPARDYNR 1293 K PF-434 S. pneumoniae (S) GQLLADKRPARDYNRK 1294 PF-437 S. pneumoniae (I) FQKPFTGEEVEDFQDDDEIPTII 1295 PF-439 S. epidermidis (C) RVLVLKKFHGIMDGNRNVAVFFVGQ 1296 E. coli (R) MRSA (M) S. pneumoniae (R) E. faecalis (C) PF-440 S. epidermidis (C) MFIISPDLFNIAVILYILFFIHDILLLILS 1297 E. coli (R) MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-442 MRSA (M) MQIFYIKTKIFLSFFLFLLIFSQCFYKIEE 1298 S. pneumoniae (C) PF-443 E. coli (R) KLLYFFNYFENLQQVHLLVQL 1299 MRSA (C) S. pneumoniae (C) PF-444 S. epidermidis (C) MAAKLWEEGKMVYASSASMTKRLKL 1300 E. coli (R) AMSKV MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-445 S. pneumoniae (M) ASMTKRLKLAMSKV 1301 PF-446 S. pneumoniae (H) SGNEKV 1302 PF-447 S. epidermidis (C) IDKSRNKDQFSHIFGLYNICSG 1303 MRSA (C) S. pneumoniae (C) E. faecalis (C) PF-448 S. pneumoniae (I) SLQSQLGPCLHDQRH 1304 PF-449 S. pneumoniae (H) MPTTKSKQKGWTNTKKASNTQ 1305 PF-450 MRSA (C) HRNLIILQRTIFI 1306 S. pneumoniae (C) E. faecalis (C) PF-451 S. epidermidis (C) MVNYIIGSYMLYREQNNNEALRKFDIT 1307 E. coli (R) LAM MRSA (C) S. pneumoniae (C) E. faecalis (C) PF-452 S. epidermidis (C) MNNWIKVAQISVTVINEVIDIMKEKQN 1308 E. coli (C) GGK MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-453 S. epidermidis (C) IIQDIAHAFGY 1309 E. coli (C) MRSA (C) S. pneumoniae (C) PF-454 S. epidermidis (C) MSVFVPVTNIFMFIMSPIFNVNLLHFKV 1310 E. coli (R) YI P. aeruginosa (H) MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-455 S. pneumoniae (A) MARNDDDIKKIKGTLGQSPEVYGERK 1311 LPYT PF-456 E. faecalis (A) TCVKPRTIN 1312 C. jejuni (A) PF-457 S. pneumoniae (M) INKYHHIA 1313 PF-458 P. aeruginosa (H) ISLIIFIMLFVVALFKCITNYKHQS 1314 MRSA (M) S. pneumoniae (M) PF-459 S. pneumoniae (H) EKRMSFNENQSHRPLL 1315 PF-460 S. epidermidis (C) MEHVLPFQNTPPNIVIIYKDFTHLKSITF 1316 E. coli (H) S MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-461 MRSA (R) MTLAIKNCSVTKCLGFGDFVNDDSDS 1317 S. pneumoniae (R) YFDA E. faecalis (A) PF-462 S. pneumoniae (H) KNKTDTL 1318 PF-464 S. pneumoniae (S) VDMVNRFLGN 1319 PF-465 S. pneumoniae (H) KPVGKALEEIADGKIEPVVPKEYLG 1320 PF-466 S. pneumoniae (H) VRKSDQ 1321 PF-467 S. pneumoniae (H) YYKDYFKEI 1322 PF-468 S. pneumoniae (H) EDNKDKKDKKDK 1323 PF-469 S. epidermidis (D) YKVNYNNIDNHFNTLRH 1324 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-470 E. faecalis (A) PYSDSYATRPHWEQHRAR 1325 C. jejuni (A) PF-471 S. epidermidis (C) MVGKIRGVTPRNDLLNANITGQLNLN 1326 E. coli (C) YRLI P. aeruginosa (A) MRSA (D) S. pneumoniae (D) E. faecalis (C) C. jejuni (D) PF-472 MRSA (C) MHISHLLDEVEQTEREKAVNVLENMN 1327 S. pneumoniae (R) GNVI E. faecalis (A) C. jejuni (R) PF-473 S. epidermidis (R) MAADIISTIGDLVKWIIDTVNKFKK 1328 E. coli (C) MRSA (C) S. pneumoniae (H) E. faecalis (R) C. jejuni (R) PF-474 S. epidermidis (C) MHRNLVLVKMEPIPHIMIIANQIGIIIEK 1329 E. coli (C) A P. aeruginosa (A) C. albicans (B) MRSA (D) S. pneumoniae (D) E. faecalis (C) C. jejuni (D) PF-475 S. epidermidis (M) MREKVRFTQAFKLFWTNYFNFKGRSR 1330 C. albicans (B) RSEY MRSA (S) S. pneumoniae (R) E. faecalis (R) C. jejuni (R) PF-476 S. pneumoniae (H) WADAQYKLCENCSE 1331 PF-477 S. pneumoniae (H) HKNKLNIPHIKS 1332 PF-478 S. epidermidis (C) HLFILKSHLKPFPPFRYTYD 1333 E. coli (C) MRSA (H) S. pneumoniae (C) PF-479 S. pneumoniae (C) AYILKRREEKNK 1334 PF-480 S. epidermidis (C) MVEILVNTAISVYIVALYTQWLSTRDN 1335 E. coli (R) LKA MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-482 S. pneumoniae (S) LVGYVRTSGTVRSYKIN 1336 PF-484 E. faecalis (A) HKKDIRKQVFKN 1337 PF-485 S. pneumoniae (A) KNSMSRSIALID 1338 PF-511 S. pneumoniae (H) VMQSLYVKPPLILVTKLAQQN 1339 PF-512 S. pneumoniae (H) SFMPEIQKNTIPTQMK 1340 PF-513 S. pneumoniae (M) SNGVGLGVGIGSGIRF-NH2 1341 PF-514 S. epidermidis (C) QRFYKLFYHIDLTNEQALKLFQVK 1342 E. coli (R) S. pneumoniae (M) E. faecalis (C) PF-515 S. pneumoniae (H) DKSTQDKDIKQAKLLAQELGL-NH2 1343 PF-516 S. pneumoniae (H) ASKQASKQASKQASKQ 1344 PF-517 S. pneumoniae (M) VKPTMTASLISTVC 1345 PF-518 S. epidermidis (C) SFYSKYSRYIDNLAGAIFLFF 1346 E. coli (R) MRSA (C) S. pneumoniae (M) E. faecalis (C) PF-519 E. coli (R) YLVYSGVLATAAAF-NH2 1347 MRSA (C) S. pneumoniae (S) E. faecalis (C) PF-520 S. pneumoniae (M) LGLTAGVAYAAQPTNQPTNQPTNQPT 1348 NQPTNQPTNQPRW-NH2 PF-521 S. pneumoniae (H) CGKLLEQKNFFLKTR 1349 PF-522 S. pneumoniae (H) FELVDWLETNLGKILKSKSA-NH2 1350 PF-524 E. coli (M) PDAPRTCYHKPILAALSRIVVTDR 1351 MRSA (C) S. pneumoniae (M) E. faecalis (C) PF-525 S. pneumoniae (H) KFSDQIDKGQDALKDKLGDL 1352 PF-526 S. epidermidis (C) VLLLFIFQPFQKQLL-NH2 1353 E. coli (R) C. albicans (C) MRSA (C) S. pneumoniae (R) PF-527 S. epidermidis (M) GSVIKKRRKRMAKKKHRKLLKKTRIQ 1354 M. luteus (S) RRRAGK B. subtilis (I) P. aeruginosa (I) C. albicans (B) MRSA (I) S. pneumoniae (H) C. jeikeium (I) C. jejuni (M) PF-528 S. epidermidis (H) LVDVVVLIRRHLPKSCS-NH2 1355 E. coli (H) C. albicans (C) MRSA (H) S. pneumoniae (R) PF-529 S. pneumoniae (H) LSEMERRRLRKRA-NH2 1356 PF-530 S. epidermidis (H) SKFKVLRKIIIKEYKGELMLSIQKQR 1357 E. coli (R) MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-531 S. epidermidis (I) YIQFHLNQQPRPKVKKIKIFL-NH2 1358 E. coli (M) P. aeruginosa (I) S. pneumoniae (C) PF-532 E. coli (C) KFIYKYKLSFIIYKILIQTLTMELNK 1359 MRSA (C) S. pneumoniae (C) E. faecalis (C) PF-533 S. epidermidis (H) KTPNDKIHKTIIIKHIIL 1360 E. coli (R) MRSA (H) S. pneumoniae (C) E. faecalis (C) PF-534 S. epidermidis (C) KYFHLFYHNIIHYSKQHLSLKVDFKN- 1361 E. coli (R) NH2 MRSA (C) S. pneumoniae (R) E. faecalis (C) PF-535 P. aeruginosa (H) NIKTRKRALKIIKQHQRSK 1362 S. pneumoniae (H) PF-536 S. epidermidis (C) MEPIPHIMIIANQIGIIIEKA 1363 E. coli (R) P. aeruginosa (H) MRSA (C) S. pneumoniae (M) E. faecalis (C) PF-537 S. pneumoniae (C) LANDYYKKTKKSW 1364 PF-538 S. pneumoniae (H) KNKKQTDILEKVKEILDKKKKTKSVG 1365 QKLY PF-539 MRSA (H) SIILTKKKRRKIPLSIDSQIYKYTFKQ 1366 S. pneumoniae (A) PF-540 S. epidermidis (H) KSILILIKVIFIGQTTIIL 1367 E. coli (R) MRSA (H) S. pneumoniae (R) PF-541 E. coli (H) RRNLNSPNIKTRKRALKIIKQHQRSK 1368 S. pneumoniae (H) PF-542 S. pneumoniae (H) KKDNPSLNDQDKNAVLNLLALAK 1369 PF-543 S. mutans (S) NILFGIIGFVVAMTAAVIVTAISIAK 1370 S. epidermidis (D) M. luteus (C) E. coli (C) MRSA (D) S. pneumoniae (D) PF-544 S. epidermidis (D) FGEKQMRSWWKVHWFHP 1371 MRSA (D) S. pneumoniae (M) E. faecalis (R) PF-545 B. subtilis (I) RESKLIAMADMIRRRI-NH2 1372 C. albicans (B) E. faecalis (H) C. jeikeium (H) PF-546 S. epidermidis (D) PIIAPTIKTQIQ 1373 E. coli (R) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jeikeium (D) PF-547 S. epidermidis (R) WSRVPGHSDTGWKVWHRW-NH2 1374 B. subtilis (I) MRSA (M) E. faecalis (R) PF-548 S. epidermidis (M) ARPIADLIHFNSTTVTASGDVYYGPG 1375 M. luteus (A) B. subtilis (C) MRSA (M) S. pneumoniae (D) C. jeikeium (R) C. jejuni (D) PF-549 B. subtilis (D) TGIGPIARPIEHGLDS 1376 MRSA (C) PF-550 B. subtilis (D) STENGWQEFESYADVGVDPRRYVPL 1377 PF-551 MRSA (C) QVKEKRREIELQFRDAEKKLEASVQAE 1378 PF-552 B. subtilis (D) ELDKADAALGPAKNLAPLDVINRS 1379 PF-553 B. subtilis (D) LTIVGNALQQKNQKLLLNQKKITSLG 1380 MRSA (M) S. pneumoniae (R) C. jeikeium (R) PF-554 B. subtilis (D) AKNFLTRTAEEIGEQAVREGNINGP 1381 PF-555 MRSA (M) EAYMRFLDREMEGLTAAYNVKLFTEA 1382 S. pneumoniae (R) IS C. jejuni (R) PF-556 S. epidermidis (A) SLQIRMNTLTAAKASIEAA 1383 M. luteus (A) B. subtilis (C) MRSA (M) S. pneumoniae (D) E. faecalis (A) C. jeikeium (D) C. jejuni (R) PF-557 B. subtilis (D) AANKAREQAAAEAKRKAEEQAR 1384 PF-558 S. epidermidis (M) ADAPPPLIVRYS 1385 B. subtilis (D) MRSA (C) S. pneumoniae (R) C. jejuni (H) PF-559 B. subtilis (C) SRPGKPGGVSIDVSRDRQDILSNYP 1386 C. jejuni (A) PF-560 B. subtilis (D) FGNPFRGFTLAMEADFKKRK 1387 MRSA (C) S. pneumoniae (R) C. jejuni (A) PF-561 B. subtilis (D) ESLEADVQAELDTEAAKYPALPASF 1388 MRSA (M) PF-562 S. epidermidis (A) TPEQWLERSTVVVTGLLNRK 1389 M. luteus (R) MRSA (M) S. pneumoniae (D) C. jejuni (R) PF-563 B. subtilis (D) RPELDNELDVVQNSASLDKLQASYN 1390 S. pneumoniae (H) C. jejuni (H) PF-564 B. subtilis (D) TIILNDQINSLQERLNKLNAETDRR 1391 MRSA (C) C. jeikeium (R) C. jejuni (R) PF-565 B. subtilis (D) RAEAEAQRQAEADAKRKAEEAARL 1392 MRSA (C) PF-566 M. luteus (D) EAQQVTQQLGADFNAITTPTATKV 1393 B. subtilis (C) MRSA (M) S. pneumoniae (D) C. jeikeium (C) C. jejuni (D) PF-567 M. luteus (C) QQRVKAVDASLSQVSTQVSGAVASA 1394 MRSA (D) S. pneumoniae (D) C. jeikeium (C) C. jejuni (D) PF-569 B. subtilis (D) KSKISEYTEKEFLEFVEDIYTNNK 1395 PF-571 B. subtilis (D) SDLLYYPNENREDSPAGVVKEVKE 1396 PF-572 B. subtilis (D) WRASKGLPGFKAG 1397 S. pneumoniae (R) PF-573 S. pneumoniae (C) EKKLIVKLIDSIGKSHEEIVGAG 1398 PF-574 B. subtilis (D) LVKSGKLESPYEHSEHLTLSQEKGLE 1399 PF-575 P. aeruginosa (A) LNFRAENKILEKIHISLIDTVEGSA 1400 S. pneumoniae (A) C. jeikeium (A) C. jejuni (R) PF-576 S. epidermidis (A) AYSGELPEPLVRKMSKEQVRSVMGK 1401 E. coli (A) MRSA (R) S. pneumoniae (C) C. jejuni (C) PF-577 S. epidermidis (A) PFETRESFRVPVIGILGGWDYFMHP 1402 E. coli (A) P. aeruginosa (A) MRSA (M) S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-578 S. mutans (D) QKANLRIGFTYTSDSNVCNLTFALLGS 1403 S. epidermidis (D) K M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (C) S. pneumoniae (D) PF-580 S. epidermidis (M) EILNNNQVIKELTMKYKTQFESNLGG 1404 M. luteus (C) WTARARR MRSA (M) S. pneumoniae (C) PF-581 MRSA (A) WTARARR 1405 S. pneumoniae (A) E. faecalis (A) C. jejuni (A) PF-582 E. faecalis (A) NLKTIEKECPFCNNKMDIKLKD 1406 PF-583 S. mutans (F) KFQGEFTNIGQSYIVSASHMSTSLNTG 1407 S. epidermidis (I) K MRSA (I) S. pneumoniae (D) PF-584 S. epidermidis (C) SYIKNLSNQKFLIAF 1408 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-585 S. epidermidis (S) DYNHLLNVVQDWVNTN 1409 MRSA (S) S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-586 S. epidermidis (C) FFNQANYFFKEF 1410 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-587 S. pneumoniae (C) ASGKYQSYLLNVYVDSKKDRLDIFDK 1411 LKAKAKFVL PF-588 E. faecalis (A) ESVEAIKAKAIK 1412 PF-589 MRSA (M) APLRIDEIRNSNVIDEVLDCAPKKQEHF 1413 S. pneumoniae (C) FVVPKIIE PF-590 C. jejuni (R) YYQAKLFPLL 1414 PF-591 S. pneumoniae (R) DLLKSLLGQDGAKNDEIIEFIKIIMEK 1415 E. faecalis (A) C. jejuni (C) PF-592 S. epidermidis (M) IMKNYKYFKLFIVKYALF 1416 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (S) PF-593 E. faecalis (A) MEISTLKKEKLHVKDELSQYLANYKK 1417 PF-594 E. faecalis (C) IVSAIV 1418 PF-595 S. epidermidis (C) LQNKIYELLYIKERSKLCS 1419 E. coli (C) MRSA (D) S. pneumoniae (R) E. faecalis (D) C. jejuni (D) PF-596 S. epidermidis (D) SKMWDKILTILILILELIRELIKL 1420 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-597 E. faecalis (A) DEIKVSDEEIEKFIKENNL 1421 PF-598 S. epidermidis (R) MKFMLEVRNKAISAYKEITRTQI 1422 E. coli (C) MRSA (D) S. pneumoniae (R) E. faecalis (R) C. jejuni (R) PF-599 S. epidermidis (M) LFEIFKPKH 1423 MRSA (C) S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-600 S. mutans (S) TKKIELKRFVDAFVKKSYENYILEREL 1424 S. epidermidis (C) KKLIKAINEELPTK M. luteus (C) E. coli (H) MRSA (M) S. pneumoniae (R) PF-601 E. faecalis (A) YRVTVKALE 1425 C. jejuni (A) PF-602 E. faecalis (A) LEKEKKEYIEKLFKTK 1426 PF-603 S. epidermidis (D) IDKLKKMNLQKLSYEVRISQDGKSIYA 1427 M. luteus (A) RIK E. coli (M) MRSA (M) S. pneumoniae (C) PF-604 E. faecalis (A) LMEQVEV 1428 PF-605 S. epidermidis (R) HYRWNTQWWKY 1429 E. coli (C) P. aeruginosa (A) C. albicans (B) MRSA (C) S. pneumoniae (D) E. faecalis (R) C. jejuni (R) PF-606 S. mutans (I) FESKILNASKELDKEKKVNTALSFNSH 1430 S. epidermidis (I) QDFAKAYQNGKI C. albicans (B) MRSA (I) S. pneumoniae (H) PF-607 S. epidermidis (M) YIESDPRKFDYIFGAIRDH 1431 MRSA (S) S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-609 MRSA (C) TEIKLDNNEYLVLNLDDILGILK 1432 S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-610 S. epidermidis (C) VFLKLKTSKIDLASIIFYP 1433 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-612 S. mutans (F) GTTLKYGLERQLKIDIHPEITIINLNGGA 1434 S. epidermidis (C) DEFAKL M. luteus (A) P. mirabilis (C) E. coli (C) MRSA (C) S. pneumoniae (C) PF-613 S. epidermidis (R) ADEFAKL 1435 MRSA (C) E. faecalis (A) PF-614 S. epidermidis (M) GLDIYA 1436 S. pneumoniae (R) E. faecalis (A) C. jejuni (R) PF-615 S. epidermidis (D) FLNRFIFYIFTVKTKSALIKNLFLD 1437 E. coli (C) MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jejuni (D) PF-616 S. epidermidis (R) IVFVVTKEKK 1438 E. faecalis (A) PF-617 C. albicans (H) PMNAAEPE 1439 S. pneumoniae (I) E. faecalis (H) PF-618 S. pneumoniae (I) KLNTLNKKDNPSLNDQDKNAVLNLLA 1440 E. faecalis (H) LAK PF-619 S. epidermidis (M) WSRVPGHSDTGWKVWHRW 1441 E. coli (C) MRSA (M) S. pneumoniae (C) PF-621 S. pneumoniae (I) PPSSFLV 1442 E. faecalis (H) PF-622 S. epidermidis (D) TREDVFSVRLINNIVNKQA 1443 MRSA (D) S. pneumoniae (M) E. faecalis (D) C. jeikeium (D) PF-623 S. epidermidis (M) VLFAVYLGALDWLFSWLTQKM 1444 MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jeikeium (R) PF-624 S. mutans (D) VFLLDSYCFVKINL 1445 S. epidermidis (D) M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (C) S. pneumoniae (D) PF-625 S. pneumoniae (H) SDSTNNARTRKKARDVTTKDIDK 1446 PF-626 S. pneumoniae (H) KYDFDDFEPEEA 1447 PF-627 S. epidermidis (H) INDLLSYFTLHEK 1448 C. albicans (B) MRSA (R) S. pneumoniae (I) E. faecalis (H) PF-629 S. epidermidis (C) GLAAIATVFALY 1449 MRSA (D) S. pneumoniae (M) E. faecalis (R) C. jeikeium (R) PF-630 MRSA (M) IPATPIIHS 1450 PF-631 S. pneumoniae (I) LIIYFSKTGNTARATRQI 1451 E. faecalis (H) PF-632 S. epidermidis (D) TTIQGVASLEKHGFRYTIIYPTRI 1452 B. subtilis (H) C. albicans (B) MRSA (D) S. pneumoniae (M) E. faecalis (D) C. jeikeium (D) PF-634 S. mutans (D) MPKARPVNHNKKKSKITIKSNFTLFYM 1453 S. epidermidis (D) FNP M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (D) S. pneumoniae (D) PF-635 S. epidermidis (M) MNAHGHSLIFQKMIVHAFAFFSKQKN 1454 C. albicans (B) YLYF MRSA (D) S. pneumoniae (D) E. faecalis (D) C. jeikeium (D) PF-636 B. subtilis (H) LVRLA 1455 C. albicans (B) S. pneumoniae (H) E. faecalis (H) PF-637 S. epidermidis (M) SRIKQDARSVRKYDRIGIFFYSFKSA 1456 MRSA (M) S. pneumoniae (M) E. faecalis (D) C. jeikeium (D) PF-638 S. epidermidis (R) TFILPK 1457 MRSA (M) S. pneumoniae (I) E. faecalis (H) PF-639 C. albicans (B) QATQIKSWIDRLLVSED 1458 MRSA (R) S. pneumoniae (I) E. faecalis (H) PF-640 C. albicans (B) MGDINRNF 1459 S. pneumoniae (I) E. faecalis (H) PF-642 MRSA (M) FTTPMIGIPAGLLGGSYYLKRREEKGK 1460 PF-643 MRSA (C) VRCRL 1461 S. pneumoniae (R) E. faecalis (R) PF-644 S. pneumoniae (H) TSGLIIGENGLNGL 1462 PF-645 C. albicans (B) SNSVQQG 1463 S. pneumoniae (I) PF-646 C. albicans (B) APASPGRRPG 1464 S. pneumoniae (H) PF-647 C. albicans (B) GTFLGQKCAAATAS 1465 S. pneumoniae (R) PF-649 E. faecalis (R) CPRYPFVDVGPAGPWRARWRVGS 1466 PF-651 S. pneumoniae (H) PRWPTGAGRHR 1467 PF-652 S. pneumoniae (A) FLAPARPDLQAQRQALAQ 1468 PF-653 S. pneumoniae (H) QSVHPLPAETPVADVI 1469 PF-654 C. albicans (B) LSGRLAGRR 1470 MRSA (R) S. pneumoniae (A) PF-655 S. epidermidis (R) DAPCFDDQFGDLKCQMC 1471 B. subtilis (H) MRSA (M) S. pneumoniae (H) PF-656 MRSA (R) RGMFVPFHDVDCVQ 1472 PF-657 S. epidermidis (C) YVANYTITQFGRDFDDRLAVAIHFA 1473 MRSA (D) S. pneumoniae (H) E. faecalis (D) C. jeikeium (D) PF-658 MRSA (R) PTTPPPTTPPEIPTGGTVIST 1474 S. pneumoniae (H) PF-659 S. epidermidis (M) TVIST 1475 B. subtilis (H) MRSA (R) S. pneumoniae (C) PF-660 S. pneumoniae (H) TDPQATAAPRRRTSPR 1476 PF-661 MRSA (R) PDEDIRRRAILPPAGPCRPMSPE 1477 PF-662 S. pneumoniae (A) GKQSRAHGPVASRREFRRKSG 1478 PF-663 S. pneumoniae (A) ATLIPRKA 1479 PF-664 S. epidermidis (M) DQLCVEYPARVSTG 1480 MRSA (R) S. pneumoniae (M) E. faecalis (R) PF-665 S. pneumoniae (H) VLRVATAVGEVPTGL 1481 PF-666 S. pneumoniae (A) PNRRSRPR 1482 PF-667 S. epidermidis (R) PAHQRLRIDQRLVADRDMVQDYES 1483 MRSA (R) S. pneumoniae (R) E. faecalis (R) PF-668 S. epidermidis (M) TNAESMALAFRGRVHMSVNIAGLT 1484 B. subtilis (A) C. albicans (A) MRSA (R) S. pneumoniae (M) E. faecalis (D) C. jeikeium (D) PF-670 B. subtilis (H) TVIVAPMHSGV 1485 S. pneumoniae (H) PF-672 S. epidermidis (I) MRFGSLALVAYDSAIKHSWPRPSSVRR 1486 B. subtilis (I) LRM C. albicans (I) MRSA (I) S. pneumoniae (I) E. faecalis (I) C. jeikeium (R) PF-675 S. pneumoniae (C) EIIPISPTRRCEMHTMSSAEYRGL 1487 E. faecalis (R) PF-677 S. epidermidis (R) TCRGAGMH 1488 MRSA (D) S. pneumoniae (D) E. faecalis (R) PF-680 MRSA (R) ADPHPTTGI 1489 PF-681 S. epidermidis (M) TALTTVGVSGARLITYCVGVEDI 1490 MRSA (M) S. pneumoniae (M) E. faecalis (R) C. jeikeium (R) PF-682 S. pneumoniae (A) RRGKSEQGLSRR 1491 PF-683 S. epidermidis (R) LWPVA 1492 MRSA (R) S. pneumoniae (H) PF-684 C. albicans (B) RKLSLASGFALWRRSLV 1493 S. pneumoniae (C) E. faecalis (A) PF-685 S. epidermidis (M) PTLWLACL 1494 MRSA (M) S. pneumoniae (M) E. faecalis (R) C. jeikeium (R) PF-686 S. epidermidis (H) LAVLMGYIGYRGWSGKRHINRQ 1495 B. subtilis (I) C. albicans (B) MRSA (M) S. pneumoniae (A) E. faecalis (R) PF-687 S. pneumoniae (A) AKRVLSLAVAPHRRQPVQGT 1496 PF-688 S. pneumoniae (A) ARNHAVIPAG 1497 PF-690 S. epidermidis (R) MIPLAGDPVSSHRTVEFGVLGTYLVSG 1498 MRSA (R) GSL S. pneumoniae (M) E. faecalis (R) PF-691 S. pneumoniae (R) HRTVEFGVLGTYLVSGGSL 1499 PF-692 MRSA (R) GVAREDPLEPDPLAPIIDDSR 1500 PF-693 S. pneumoniae (A) PDPAR 1501 PF-694 MRSA (R) DLIRPLYSMSAPSVA 1502 S. pneumoniae (A) PF-695 MRSA (R) ALSVMLGNIPLVVPNANQL 1503 S. pneumoniae (C) E. faecalis (R) PF-696 S. pneumoniae (H) IRSGISAAYARPLR 1504 PF-697 C. albicans (H) RADARAK 1505 S. pneumoniae (H) PF-698 C. albicans (H) SSGRAGVKCRRPTGR 1506 S. pneumoniae (A) E. faecalis (A) PF-699 S. pneumoniae (A) GRAGVKCRRPTGR 1507 PF-700 S. pneumoniae (C) LNWPFTGR 1508 PF-702 S. pneumoniae (H) LSGRLAGRR 1509 PF-704 S. pneumoniae (C) APAARAAL 1510 PF-737 S. pneumoniae (D) KSSGSSASASSTAGGSSSK 1511 PF-738 MRSA (M) KSGATSAASGAKSGASS 1512 PF-741 S. mutans (D) AKREDTVAAQIGANILNLIQ 1513 S. epidermidis (C) M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (C) S. pneumoniae (D) PF-744 S. pneumoniae (H) LGVGTFVGKVLIKNQQKQKSKKKAQ 1514 PF-745 S. mutans (D) ANSQNSLFSNRSSFKSIFDKKSNITTNA 1515 M. luteus (C) TTPNSNIIIN MRSA (C) S. pneumoniae (C) PF-746 S. mutans (D) FLGNSQYFTRK 1516 S. epidermidis (C) M. luteus (C) E. coli (C) P. aeruginosa (A) MRSA (C) S. pneumoniae (C) PF-748 S. pneumoniae (H) FQGFFDVAVNKWWEEHNKAKLWKN 1517 VKGKFLEGEGEEEDDE PF-749 S. pneumoniae (H) GVNKWWEEHNKAKLWKNVKGKFLE 1518 GEGEEEDDE PF-752 S. pneumoniae (C) LHVIRPRPELSELKFPITKILKVNKQGL 1519 KK PF-756 S. pneumoniae (A) DALLRLA 1520 PF-757 S. pneumoniae (H) PQAISSVQQNA 1521 PF-760 S. epidermidis (M) DHITLDDYEIHDGFNFELYYG 1522 MRSA (M) S. pneumoniae (C) PF-761 S. mutans (D) SKFELVNYASGCSCGADCKCASETECK 1523 S. epidermidis (C) CASKK M. luteus (C) E. coli (C) P. aeruginosa (C) MRSA (D) S. pneumoniae (C) PF-762 S. pneumoniae (H) PAPAPSAPAPAPEQPEQPA 1524 PF-763 S. epidermidis (M) GIWMARNYFHRSSIRKVYVESDKEYE 1525 M. luteus (C) RVHPMQKIQYEGNYKSQ MRSA (D) S. pneumoniae (C) PF-764 MRSA (D) GYFEPGKRD 1526 S. pneumoniae (H) PF-770 S. mutans (D) GVGIGFIMMGVVGYAVKLVHIPIRYLI 1527 S. epidermidis (D) V M. luteus (C) P. mirabilis (C) E. coli (C) MRSA (D) S. pneumoniae (C) PF-776 S. mutans (D) VSILLYLSATIILPNVLRLLVARAIIVRV 1528 S. epidermidis (D) M. luteus (C) E. coli (C) MRSA (D) S. pneumoniae (C) PF-C052 P. gingivalis (H) SRFRNGV 1529 PF-C055 F. nucleatum (T) YNLSIYIYFLHTITIAGLITLPFII 1530 S. mutans (I) PF-C057 S. mutans (I) YFWWYWVQDCIPYKNNEVWLELSNN 1531 MK PF-C058 S. mutans (F) FETGFGDGYYMSLWGLNEKDEVCKV 1532 VIPFINPELID PF-C061 F. nucleatum (T) TLNYKKMFFSVIFLLGLNYLICNSPLFF 1533 S. mutans (F) KQIEF PF-C062 F. nucleatum (T) PLARATEVVATLFIICSLLLYLTR 1534 S. mutans (I) PF-C064 F. nucleatum (T) DEEALEMGANLYAQFAIDFLNSKK 1535 PF-C065 F. nucleatum (T) DEERYSDSYFLKEKVFYLILALFLILFH 1536 QKYLYFLEIITI PF-C069 F. nucleatum (T) NALMLREMQLAKNIKVEVTDVLSNKK 1537 YC PF-C071 F. nucleatum (T) QVIVKIL 1538 PF-C072 F. nucleatum (T) KKMFSLIRKVNWIFFILFIVLDLTNVFP 1539 P. gingivalis (T) LIRTILFAILSRQ S. mutans (F) PF-C075 F. nucleatum (T) KALVISVFAIVFSIIFVKFFYWRDKK 1540 P. gingivalis (R) S. mutans (F) PF-C084 F. nucleatum (T) FFSVIFLFGLNYLICNSPLFNILR 1541 P. gingivalis (R) S. mutans (F) PF-C085 S. mutans (F) KKFKIFVIINWFYHKYIILNFEENF 1542 PF-C086 F. nucleatum (T) ELFFTILSDCNELFLLHLLQQPLFYIKK 1543 GK PF-C088 F. nucleatum (H) DIANNILNSVSERLIIA 1544 P. gingivalis (R) S. mutans (I) PF-C089 P. gingivalis (R) MPKRHYYKLEAKALQFGLPFAYSPIQL 1545 LK PF-C091 F. nucleatum (T) ASNTPRFVRLTLFNFYSKIWNVTHLFLF 1546 NNL PF-C095 F. nucleatum (T) LLALNMNEDTYYFELFFIFDNQNKKW 1547 LIFDLKERG PF-C098 F. nucleatum (T) PETKGKVSAFVFGIVVANVIAVVYILY 1548 S. mutans (F) MLREIGIIQ PF-C120 F. nucleatum (T) ASLSTMTFKVMELKELIILLCGLTMLMI 1549 QTEFV PF-C131 F. nucleatum (T) QWIVAKREIRMHIYCHISVIHVIIFFG 1550 S. mutans (F) PF-C135 F. nucleatum (C) KNTHAYLRVLRLSSLILSYQASVYPLF 1551 S. mutans (F) AYLCQQKDY PF-C136 F. nucleatum (C) LILSYQASVYPLFAYLCQQKDY 1552 P. gingivalis (R) PF-C137 F. nucleatum (T) QRMYWFKRGFETGDFSAGDTFAELK 1553 PF-C139 S. mutans (F) LLASHPERLSLGVFFVYRVLHLLLENT 1554 PF-C142 S. mutans (I) DFPPLSFFRRRFHAYTAPIDNFFGANPF 1555 PF-C143 F. nucleatum (C) VVFGGGDRLV 1556 PF-C145 F. nucleatum (C) YGKESDP 1557 S. mutans (I) PF-C180 P. gingivalis (R) TVEELDKAFTWGAAAALAIGVIAINVG 1558 S. mutans (S) LAAGYCYNNNDVF PF-C181 F. nucleatum (T) KMRAGQVVFIYKLILVLLFYVLQKLFD 1559 LKKGCF PF-C194 F. nucleatum (T) NTNDLLQAFELMGLGMAGVFIVLGILY 1560 P. gingivalis (T) IVAELLIKIFPVNN S. mutans (F) PF-C214 F. nucleatum (T) GGHKQLVIEPLVSQ 1561 PF-C281 S. mutans (F) KKEKLLTAIRLQHRAEIRGYFTIFFLFFR 1562 I PF-C290 S. mutans (F) GNVHPESDFHNLIQFIKTFLYFTIFFKYF 1563 L PF-C291 F. nucleatum (T) HPFLTGTGCPLFLIFRLFFVKAYFSFTVF 1564 S. mutans (F) PF-C293 F. nucleatum (T) IIIILPKIYLVCKTV 1565 P. gingivalis (R) S. mutans (F) PF-S003 S. epidermidis (R) ALALLKQDLLNFEGRGRIITSTYLQFNE 1566 M. luteus (R) GCVP B. subtilis (A) P. aeruginosa (A) C. albicans (A) MRSA (M) S. pneumoniae (D) C. jeikeium (D) C. jejuni (D) Key to Abbreviations: (A) Peptide aggregates; (B) Less hyphal formation; (C) Clumps; (D) Diffuse clumps and small polyps; (F) Diffuse growth; (H) Thin; (I) Growth inhibition; (M) Microcolony formation; (R) Rippled; (S) Small polyps; (T) Thick; (W) Halo formation on top, microlonies on bottom. These data thus indicate peptide-mediated interruption of bacterial biofilm formation processes, cellular metabolism, cellular import/export, nutrient acquisition, quorum sensing and communication, motility, chemotaxis, replication, translation, and/or transcription. Accordingly, without being bound to a particular theory, it is believed that the alteration of one or more of these basic pathways is important to pathogenesis, or the stopping thereof.

In certain embodiments, the amino acid sequence of the antimicrobial peptides comprises or consists of a single amino acid sequence, e.g., as listed above in Tables 4 and/or 5, and/or Table 15, and/or below in Table 14. In certain embodiments the amino acid sequence of the antimicrobial peptides comprises two copies, three copies, four copies, five copies six copies or more of one or more of the amino acid sequences listed in Tables 4, and/or 5, and/or Table 15, and/or Table 14. Thus, compound antimicrobial constructs are contemplated where the construct comprises multiple domains each having antimicrobial activity. The AMP domains comprising such a construct can be the same or different. In certain embodiments the construct comprises at least 2, at least 3, at least 4, at least 5, at least 6, at least 7, or at least 8 different AMP domains each domain comprising a different AMP sequence.

Various AMP domains comprising such a construct can be joined directly to each other or two or more of such domains can be attached to each other via a linker. An illustrative, but non-limiting, list of suitable linkers is provided in Table 16. Thus, in certain embodiments, two or more AMP domains comprising a compound AMP construct are chemically conjugated together.

In certain embodiments the two or more AMP domains comprising the AMP construct are joined by a peptide linker. Where all the AMP domains are attached directly to each other or are joined by peptide linkers, the entire construct can be provided as a single-chain peptide (fusion protein).

In various embodiments, the antimicrobial peptides described herein comprise one or more of the amino acid sequences shown in Tables 4, and/or 5, and/or 15 and/or 14 (and/or the retro, inverso, retroinverso, etc. forms of such sequences). In certain embodiments the peptides range in length up to about 100 amino acids in length, preferably up to about 80, about 70, about 60, or about 51 amino acids in length. In certain embodiments the peptides range in length from about 8 amino acids up to about 100 amino acids 80 amino acids, 60 amino acids or about 51 amino acids in length. In certain embodiments the peptides range in length from about 8 up to about 50, 40, 30, 20, 15, 15, 13, or 12 amino acids in length.

As shown in Tables 4, and/or 5, and/or 15 and/or 14, the various amino acid sequences described herein are effective against particular microorganisms. The range of activity of the peptides or compositions comprising such peptides can be increased by including amino acid sequences effective against different microorganisms either as separate components and/or as multiple domains within a single construct.

TABLE 6 Illustrative target microorganisms and peptides effective against that target. Gram Positive Bacteria: A. naeslundii PF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, PF-148 B. subtilis PF-002, PF-005, PF-006, PF-040, PF-053, PF-056, PF-061, PF-063, PF-067, PF-068, PF-069, PF-070, PF-071, PF-145, PF-148, PF-171, PF-175, PF-283, PF-289, PF-292, PF-296, PF-297, PF-301, PF-303, PF-305, PF-306, PF-307, PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-497, PF-499, PF-527, PF-531, PF-545, PF-547, PF-548, PF-549, PF-550, PF-552, PF-553, PF-554, PF-556, PF-557, PF-558, PF-559, PF-560, PF-561, PF-563, PF-564, PF-565, PF-566, PF-569, PF-571, PF-572, PF-574, PF-632, PF-636, PF-655, PF-659, PF-668, PF-670, PF-672, PF-686, PF-998, PF-2003 C. difficile PF-522, PF-531, PF-538 C. jeikeium PF-001, PF-003, PF-004, PF-101, PF-011, PF-012, PF-013, PF-021, PF-022, PF-025, PF-028, PF-030, PF-032, PF-033, PF-036, PF-037, PF-040, PF-042, PF-043, PF-046, PF-048, PF-052, PF-053, PF-056, PF-057, PF-063, PF-065, PF-067, PF-068, PF-073, PF-075, PF-076, PF-099, PF-124, PF-127, PF-129, PF-133, PF-135, PF-137, PF-139, PF-140, PF-145, PF-148, PF-164, PF-173, PF-176, PF-186, PF-188, PF-190, PF-191, PF-196, PF-199, PF-203, PF-204, PF-208, PF-527, PF-531, PF-545, PF-546, PF-548, PF-553, PF-556, PF-564, PF-566, PF-567, PF-575, PF-622, PF-523, PF-629, PF-632, PF-635, PF-637, PF-657, PF-668, PF-672, PF-681, PF-685, PF-S003 E. faecalis PF-007, PF-053, PF-057, PF-068, PF-347, PF-349, PF-355, PF-356, PF-363, PF-366, PF-369, PF-374, PF-375, PF-376, PF-379, PF-380, PF-381, PF-386, PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-396, PF-398, PF-399, PF-401, PF-407, PF-410, PF-411, PF-418, PF-422, PF-425, PF-426, PF-427, PF-429, PF-431, PF-432, PF-439, PF-440, PF-444, PF-447, PF-450, PF-451, PF-452, PF-454, PF-456, PF-460, PF-461, PF-469, PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-480, PF-484, PF-514, PF-518, PF-519, PF-524, PF-530, PF-532, PF-533, PF-534, PF-536, PF-544, PF-545, PF-546, PF-547, PF-556, PF-577, PF-581, PF-582, PF-584, PF-585, PF-586, PF-588, PF-591, PF-592, PF-593, PF-594, PF-595, PF-596, PF-597, PF-598, PF-599, PF-601, PF-602, PF-604, PF-605, PF-607, PF-609, PF-610, PF-613, PF-614, PF-615, PF-616, PF-617, PF-618, PF-621, PF-622, PF-623, PF-627, PF-629, PF-631, PF-632, PF-635, PF-636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-649, PF-657, PF-664, PF-667, PF-668, PF-672, PF-675, PF-677, PF-681, PF-684, PF-685, PF-686, PF-690, PF-695, PF-698 M. luteus PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-012, PF-013, PF-020, PF-021, PF-022, PF-025, PF-030, PF-036, PF-037, PF-040, PF-042, PF-043, PF-051, PF-052, PF-053, PF-056, PF-057, PF-063, PF-067, PF-068, PF-071, PF-073, PF-075, PF-076, PF-125, PF-127, PF-137, PF-139, PF-140, PF-145, PF-148, PF-171, PF-175, PF-176, PF-199, PF-204, PF-212, PF-215, PF-224, PF-226, PF-234, PF-235, PF-249, PF-250, PF-255, PF-257, PF-264, PF-270, PF-271, PF-274, PF-276, PF-278, PF-357, PF-527, PF-543, PF-548, PF-556, PF-562, PF-566, PF-567, PF-578, PF-580, PF-600, PF-603, PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF-761, PF-763, PF-770, PF-776, PF-S003 MRSA PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-011, PF-012, PF-013, PF-015, PF-017, PF-019, PF-020, PF-021, PF-022, PF-023, PF-024, PF-025, PF-026, PF-027, PF-028, PF-029, PF-030, PF-031, PF-033, PF-035, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-045, PF-046, PF-048, PF-049, PF-051, PF-052, PF-053, PF-056, PF-057, PF-058, PF-063, PF-064, PF-065, PF-066, PF-067, PF-068, PF-071, PF-073, PF-074, PF-075, PF-076, PF-140, PF-145, PF-148, PF-149, PF-156, PF-168, PF-171, PF-178, PF-191, PF-209, PF-347, PF-349, PF-350, PF-354, PF-355, PF-356, PF-357, PF-360, PF-362, PF-366, PF-369, PF-370, PF-373, PF-374, PF-375, PF-376, PF-378, PF-379, PF-380, PF-381, PF-382, PF-386, PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-395, PF-396, PF-398, PF-399, PF-401, PF-403, PF-404, PF-405, PF-406, PF-407, PF-408, PF-410, PF-411, PF-413, PF-417, PF-418, PF-422, PF-425, PF-426, PF-427, PF-429, PF-430, PF-431, PF-432, PF-439, PF-440, PF-442, PF-443, PF-444, PF-447, PF-450, PF-451, PF-452, PF-453, PF-454, PF-458, PF-460, PF-461, PF-469, PF-471, PF-472, PF-473, PF-474, PF-475, PF-478, PF-480, PF-518, PF-519, PF-524, PF-526, PF-527, PF-528, PF-530, PF-532, PF-533, PF-534, PF-536, PF-539, PF-540, PF-543, PF-544, PF-545, PF-546, PF-547, PF-548, PF-549, PF-551, PF-553, PF-555, PF-556, PF-558, PF-560, PF-561, PF-562, PF-564, PF-565, PF-566, PF-567, PF-576, PF-577, PF-578, PF-580, PF-581, PF-583, PF-584, PF-585, PF-586, PF-589, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-613, PF-615, PF-619, PF-622, PF-623, PF-624, PF-627, PF-629, PF-630, PF-632, PF-634, PF-635, PF-637, PF-638, PF-639, PF-652, PF-643, PF-654, PF-655, PF-656, PF-657, PF-658, PF-659, PF-661, PF-664, PF-667, PF-778, PF-672, PF-677, PF-680, PF-683, PF-685, PF-686, PF-690, PF-692, PF-694, PF-695, PF-738, PF-741, PF-745, PF-746, PF-760, PF-761, PF-763, PF-764, PF-770, PF-776, PF-S003 S. PF-001, PF-003, PF-004, PF-006, PF-007, PF-009, PF-010, PF-012, PF-013, epidermidis PF-020, PF-021, PF-022, PF-024, PF-025, PF-027, PF-028, PF-030, PF-032, PF-033, PF-034, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-046, PF-048, PF-051, PF-052, PF-953, PF-956, PF-957, PF-961, PF-963, PF-964, PF-965, PF-967, PF-968, PF-971, PF-073, PF-074, PF-075, PF-076, PF-099, PF-123, PF-124, PF-125, PF-127, PF-128, PF-129, PF-137, PF-139, PF-140, PF-145, PF-148, PF-153, PF-157, PF-171, PF-173, PF-176, PF-178, PF-180, PF-186, PF-190, PF-191, PF-192, PF-196, PF-199, PF-203, PF-204, PF-208, PF-209, PF-226, PF-233, PF-273, PF-278, PF-283, PF-290, PF-292, PF-293, PF-294, PF-296, PF-297, PF-301, PF-307, PF-310, PF-313, PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-347, PF-349, PF-350, PF-355, PF-356, PF-357, PF-360, PF-363, PF-366, PF-369, PF-370, PF-373, PF-374, PF-375, PF-376, PF-378, PF-379, PF-380, PF-381, PF-383, PF-386, PF-387, PF-389, PF-390, PF-393, PF-395, PF-396, PF-397, PF-398, PF-399, PF-401, PF-403, PF-404, PF-406, PF-407, PF-408, PF-410, PF-411, PF-413, PF-417, PF-418, PF-422, PF-425, PF-246, PF-249, PF-430, PF-431, PF-432, PF-439, PF-440, PF-444, PF-447, PF-451, PF-452, PF-453, PF-454, PF-460, PF-469, PF-471, PF-473, PF-474, PF-475, PF-478, PF-480, PF-514, PF-518, PF-526, PF-527, PF-528, PF-530, PF-531, PF-533, PF-534, PF-536, PF-540, PF-543, PF-544, PF-546, PF-547, PF-548, PF-556, PF-558, PF-562, PF-576, PF-577, PF-578, PF-580, PF-583, PF-584, PF-585, PF-586, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-610, PF-612, PF-613, PF-614, PF-615, PF-616, PF-619, PF-622, PF-623, PF-624, PF-627, PF-632, PF-634, PF-635, PF-637, PF-638, PF-655, PF-657, PF-659, PF-664, PF-667, PF-778, PF-672, PF-677, PF-681, PF-683, PF-685, PF-686, PF-690, PF-741, PF-746, PF-760, PF-761, PF-763, PF-770, PF-776, PF-S003 S. mutans G-1, G-2, G-4, G-8, PF-020, PF-040, PF-051, PF-531, PF-543, PF-547, PF-578, PF-583, PF-600, PF-606, PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF-761, PF-770, PF-776, PF-0055, PF-0057, PF-0058, PF-C061, PF-0062, PF-0072, PF-0075, PF-0084, PF-0085, PF-0088, PF-C098, PF-C131, PF-C135, PF-C139, PF-C142, PF-C146, PF-C180, PF-C194, PF-C281, PF-C290, PF-C291, PF-C293 S. PF-002, PF-005, PF-006, PF-020, PF-033, PF-040, PF-051, PF-053, PF-056, pneumoniae PF-057, PF-061, PF-063, PF-068, PF-071, PF-073, PF-140, PF-144, PF-145, PF-148, PF-171, PF-175, PF-178, PF-220, PF-355, PF-356, PF-357, PF-363, PF-366, PF-380, PF-389, PF-390, PF-393, PF-407, PF-411, PF-414, PF-415, PF-416, PF-417, PF-418, PF-419, PF-421, PF-422, PF-423, PF-424, PF-425, PF-426, PF-427, PF-428, PF-429, PF-430, PF-431, PF-432, PF-433, PF-434, PF-437, PF-439, PF-440, PF-442, PF-443, PF-444, PF-445, PF-446, PF-447, PF-448, PF-449, PF-450, PF-451, PF-452, PF-453, PF-454, PF-455, PF-457, PF-458, PF-469, PF-460, PF-461, PF-462, PF-464, PF-465, PF-466, PF-467, PF-468, PF-469, PF-471, PF-472, PF-473, PF-474, PF-475, PF-476, PF-477, PF-478, PF-479, PF-480, PF-482, PF-485, PF-511, PF-512, PF-513, PF-514, PF-515, PF-516, PF-517, PF-518, PF-519, PF-520, PF-521, PF-522, PF-523, PF-524, PF-525, PF-526, PF-527, PF-528, PF-529, PF-530, PF-531, PF-532, PF-533, PF-534, PF-535, PF-536, PF-537, PF-538, PF-539, PF-540, PF-541, PF-542, PF-543, PF-544, PF-546, PF-548, PF-553, PF-555, PF-556, PF-558, PF-560, PF-562, PF-563, PF-566, PF-567, PF-572, PF-573, PF-575, PF-576, PF-577, PF-578, PF-580, PF-581, PF-583, PF-585, PF-585, PF-586, PF-587, PF-589, PF-591, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-614, PF-615, PF-617, PF-618, PF-619, PF-621, PF-622, PF-623, PF-624, PF-625, PF-626, PF-627, PF-629, PF-631, PF-632, PF-634, PF-635, PF-636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-644, PF-645, PF-646, PF-647, PF-651, PF-652, PF-653, PF-654, PF-655, PF-657, PF-658, PF-659, PF-660, PF-662, PF-663, PF-664, PF-665, PF-666, PF-667, PF-668, PF-670, PF-672, PF-675, PF-677, PF-681, PF-682, PF-683, PF-684, PF-685, PF-686, PF-687, PF-688, PF-690, PF-691, PF-693, PF-694, PF-695, PF-696, PF-697, PF-698, PF-699, PF-700, PF-702, PF-704, PF-737, PF-741, PF-744, PF-745, PF-746, PF-748, PF-749, PF-752, PF-756, PF-757, PF-760, PF-761, PF-762, PF-763, PF-764, PF-770, PF-776, PF-S003 Gram Negative Bacteria: A. baumannii PF-531, PF-006, PF-538, PF-530 C. jejuni PF-006, PF-008, PF-033, PF-040, PF-053, PF-056, PF-057, PF-059, PF-061, PF-063, PF-067, PF-068, PF-069, PF-071, PF-073, PF-140, PF-145, PF-148, PF-171, PF-175, PF-355, PF-356, PF-363, PF-366, PF-380, PF-389, PF-390, PF-392, PF-393, PF-411, PF-418, PF-422, PF-425, PF-426, PF-431, PF-432, PF-456, PF-469, PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-527, PF-548, PF-555, PF-556, PF-558, PF-559, PF-560, PF-562, PF-563, PF-564, PF-566, PF-567, PF-575, PF-576, PF-577, PF-581, PF-584, PF-585, PF-586, PF-590, PF-591, PF-592, PF-595, PF-596, PF-598, PF-599, PF-601, PF-605, PF-607, PF-609, PF-610, PF-614, PF-615, PF-S003 E. coli PF-007, PF-040, PF-053, PF-057, PF-068, PF-178, PF-344, PF-347, PF-349, PF-350, PF-355, PF-360, PF-362, PF-363, PF-366, PF-369, PF-370, PF-374, PF-375, PF-376, PF-379, PF-380, PF-381, PF-383, PF-385, PF-386, PF-387, PF-390, PF-395, PF-396, PF-398, PF-399, PF-401, PF-403, PF-410, PF-411, PF-413, PF-418, PF-425, PF-426, PF-427, PF-432, PF-439, PF-440, PF-443, PF-444, PF-451, PF-452, PF-453, PF-454, PF-460, PF-469, PF-471, PF-473, PF-474, PF-478, PF-480, PF-514, PF-518, PF-519, PF-524, PF-526, PF-528, PF-530, PF-531, PF-532, PF-533, PF-534, PF-536, PF-540, PF-541, PF-543, PF-546, PF-576, PF-577, PF-578, PF-584, PF-586, PF-592, PF-595, PF-596, PF-598, PF-600, PF-603, PF-605, PF-606, PF-610, PF-612, PF-615, PF-619, PF-624, PF-634, PF-741, PF-746, PF-761, PF-770, PF-776 F. nucleatum PF-0055, PF-0061, PF-0062, PF-0064, PF-0065, PF-0069, PF-0071, PF-0072, PF-0075, PF-0084, PF-0086, PF-0088, PF-0091, PF-0095, PF-0098, PF-C120, PF-C131, PF-C135, PF-C136, PF-C137, PF-C143, PF-C145, PF-C181, PF- C194, PF-C214, PF-C291, PF-C293 M. xanthus G-5, G-6, G-7 P. PF-053, PF-063, PF-067, PF-128, PF-140, PF-143, PF-168, PF-204, PF-209, aeruginosa PF-355, PF-356, PF-366, PF-380, PF-411, PF-425, PF-432, PF-454, PF-458, PF-471, PF-474, PF-527, PF-531, PF-535, PF-536, PF-575, PF-577, PF-605, PF-746, PF-761, PF-S003 P. gingivalis PF-0052, PF-0072, PF-0075, PF-0084, PF-0088, PF-0089, PF-C136, PF-C180, PF-C194, C293 P. mirabilis PF-040, PF-578, PF-612, PF-624, PF-634, PF-741, PF-770 Yeast Fungi: A. niger PF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, PF-148 C. albicans PF-053, PF-056, PF-057, PF-071, PF-140, PF-148, PF-175, PF-278, PF-307, PF-425, PF-426, PF-474, PF-475, PF-526, PF-527, PF-528, PF-545, PF-605, PF-606, PF-617, PF-627, PF-632, PF-635, PF-636, PF-639, PF-640, PF-645, PF-646, PF-647, PF-654, PF-668, PF-672, PF-684, PF-686, PF-697, PF-698, PF-S003 T. rubrum PF-283, PF-307, PF-527, PF-531, PF-547, PF-672

In certain embodiments the activity against a particular microorganism or group of microorganisms can be increased by increasing the number of peptides or peptide domains with activity against that microorganism or group of microorganisms.

Thus, for example, in certain embodiments, a peptide or composition effective to kill or inhibit the growth and/or proliferation of a yeast or fungus can comprise or more peptides and/or one or more peptide domains having sequences selected from the sequences shown in Tables 4, 5, or 6 (e.g., PF-S003, PF-053, PF-056, PF-057, PF-071, PF-140, PF-148, PF-168, PF-175, PF-278, PF-283, PF-307, PF-425, PF-426, PF-448, PF-474, PF-475, PF-525, PF-526, PF-527, PF-528, PF-529, PF-531, PF-545, PF-547, PF-606, PF-617, PF-627, PF-632, PF-635, PF-636, PF-639, PF-640, PF-645, PF-646, PF-647, PF-654, PF-668, PF-672, PF-684, PF-686, PF-697, and PF-69)₈. A peptide or composition effective to kill or inhibit the growth and/or proliferation of Aspergillus niger can comprise one or more peptides and/or one or more peptide domains having sequences selected from the group consisting of PF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, and PF-148. A peptide or composition effective to kill or inhibit the growth and/or proliferation of Candida albicans can comprise one or more peptides and/or one or more peptide domains having sequences selected from the group consisting of PF-053, PF-056, PF-057, PF-071, PF-140, PF-148, PF-175, PF-278, PF-307, PF-425, PF-426, PF-474, PF-475, PF-526, PF-527, PF-528, PF-545, PF-605, PF-606, PF-617, PF-627, PF-632, PF-635, PF-636, PF-639, PF-640, PF-645, PF-646, PF-647, PF-654, PF-668, PF-672, PF-684, PF-686, PF-697, PF-698, and PF-S003. A peptide or composition effective to kill or inhibit the growth and/or proliferation of Trichophyton rubrum can comprise one or more peptides and/or one or more peptide domains having sequences selected from the group consisting of PF-283, PF-307, PF-527, PF-531, PF-547, and PF-672.

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of a bacterium can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against a bacterium in Tables 4, 5, or 6.

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of a gram positive bacterium can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against a gram positive bacterium in Tables 4, 5, or 6. In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of a gram negative bacterium can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against a gram negative bacterium in Tables 4, 5, or 6.

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of A. naeslundii can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against A. Naeslundii in Tables 4, 5, or 6 (e.g., from the group consisting of PF-531, PF-527, PF-672, PF-545, PF-168, PF-448, PF-525, PF-529, and PF-148).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of B. subtilis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against B. subtilis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-002, PF-005, PF-006, PF-040, PF-053, PF-056, PF-061, PF-063, PF-067, PF-068, PF-069, PF-070, PF-071, PF-145, PF-148, PF-171, PF-175, PF-283, PF-289, PF-292, PF-296, PF-297, PF-301, PF-303, PF-305, PF-306, PF-307, PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-497, PF-499, PF-527, PF-531, PF-545, PF-547, PF-548, PF-549, PF-550, PF-552, PF-553, PF-554, PF-556, PF-557, PF-558, PF-559, PF-560, PF-561, PF-563, PF-564, PF-565, PF-566, PF-569, PF-571, PF-572, PF-574, PF-632, PF-636, PF-655, PF-659, PF-668, PF-670, PF-672, PF-686, PF-998, and PF-2003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of C. difficile can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against C. difficile in Tables 4, 5, or 6 (e.g., from the group consisting of PF-522, PF-531, and PF-538).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of C. jeikeium can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against C. jeikeium in Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-101, PF-011, PF-012, PF-013, PF-021, PF-022, PF-025, PF-028, PF-030, PF-032, PF-033, PF-036, PF-037, PF-040, PF-042, PF-043, PF-046, PF-048, PF-052, PF-053, PF-056, PF-057, PF-063, PF-065, PF-067, PF-068, PF-073, PF-075, PF-076, PF-099, PF-124, PF-127, PF-129, PF-133, PF-135, PF-137, PF-139, PF-140, PF-145, PF-148, PF-164, PF-173, PF-176, PF-186, PF-188, PF-190, PF-191, PF-196, PF-199, PF-203, PF-204, PF-208, PF-527, PF-531, PF-545, PF-546, PF-548, PF-553, PF-556, PF-564, PF-566, PF-567, PF-575, PF-622, PF-523, PF-629, PF-632, PF-635, PF-637, PF-657, PF-668, PF-672, PF-681, PF-685, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of E. faecalis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against E. faecalis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-007, PF-053, PF-057, PF-068, PF-347, PF-349, PF-355, PF-356, PF-363, PF-366, PF-369, PF-374, PF-375, PF-376, PF-379, PF-380, PF-381, PF-386, PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-396, PF-398, PF-399, PF-401, PF-407, PF-410, PF-411, PF-418, PF-422, PF-425, PF-426, PF-427, PF-429, PF-431, PF-432, PF-439, PF-440, PF-444, PF-447, PF-450, PF-451, PF-452, PF-454, PF-456, PF-460, PF-461, PF-469, PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-480, PF-484, PF-514, PF-518, PF-519, PF-524, PF-530, PF-532, PF-533, PF-534, PF-536, PF-544, PF-545, PF-546, PF-547, PF-556, PF-577, PF-581, PF-582, PF-584, PF-585, PF-586, PF-588, PF-591, PF-592, PF-593, PF-594, PF-595, PF-596, PF-597, PF-598, PF-599, PF-601, PF-602, PF-604, PF-605, PF-607, PF-609, PF-610, PF-613, PF-614, PF-615, PF-616, PF-617, PF-618, PF-621, PF-622, PF-623, PF-627, PF-629, PF-631, PF-632, PF-635, PF-636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-649, PF-657, PF-664, PF-667, PF-668, PF-672, PF-675, PF-677, PF-681, PF-684, PF-685, PF-686, PF-690, PF-695, and PF-698).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of M. luteus can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against M. luteus in Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-012, PF-013, PF-020, PF-021, PF-022, PF-025, PF-030, PF-036, PF-037, PF-040, PF-042, PF-043, PF-051, PF-052, PF-053, PF-056, PF-057, PF-063, PF-067, PF-068, PF-071, PF-073, PF-075, PF-076, PF-125, PF-127, PF-137, PF-139, PF-140, PF-145, PF-148, PF-171, PF-175, PF-176, PF-199, PF-204, PF-212, PF-215, PF-224, PF-226, PF-234, PF-235, PF-249, PF-250, PF-255, PF-257, PF-264, PF-270, PF-271, PF-274, PF-276, PF-278, PF-357, PF-527, PF-543, PF-548, PF-556, PF-562, PF-566, PF-567, PF-578, PF-580, PF-600, PF-603, PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF-761, PF-763, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of MRSA can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against MRSA in Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-006, PF-007, PF-010, PF-011, PF-012, PF-013, PF-015, PF-017, PF-019, PF-020, PF-021, PF-022, PF-023, PF-024, PF-025, PF-026, PF-027, PF-028, PF-029, PF-030, PF-031, PF-033, PF-035, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-045, PF-046, PF-048, PF-049, PF-051, PF-052, PF-053, PF-056, PF-057, PF-058, PF-063, PF-064, PF-065, PF-066, PF-067, PF-068, PF-071, PF-073, PF-074, PF-075, PF-076, PF-140, PF-145, PF-148, PF-149, PF-156, PF-168, PF-171, PF-178, PF-191, PF-209, PF-347, PF-349, PF-350, PF-354, PF-355, PF-356, PF-357, PF-360, PF-362, PF-366, PF-369, PF-370, PF-373, PF-374, PF-375, PF-376, PF-378, PF-379, PF-380, PF-381, PF-382, PF-386, PF-387, PF-389, PF-390, PF-392, PF-393, PF-394, PF-395, PF-396, PF-398, PF-399, PF-401, PF-403, PF-404, PF-405, PF-406, PF-407, PF-408, PF-410, PF-411, PF-413, PF-417, PF-418, PF-422, PF-425, PF-426, PF-427, PF-429, PF-430, PF-431, PF-432, PF-439, PF-440, PF-442, PF-443, PF-444, PF-447, PF-450, PF-451, PF-452, PF-453, PF-454, PF-458, PF-460, PF-461, PF-469, PF-471, PF-472, PF-473, PF-474, PF-475, PF-478, PF-480, PF-518, PF-519, PF-524, PF-526, PF-527, PF-528, PF-530, PF-532, PF-533, PF-534, PF-536, PF-539, PF-540, PF-543, PF-544, PF-545, PF-546, PF-547, PF-548, PF-549, PF-551, PF-553, PF-555, PF-556, PF-558, PF-560, PF-561, PF-562, PF-564, PF-565, PF-566, PF-567, PF-576, PF-577, PF-578, PF-580, PF-581, PF-583, PF-584, PF-585, PF-586, PF-589, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-613, PF-615, PF-619, PF-622, PF-623, PF-624, PF-627, PF-629, PF-630, PF-632, PF-634, PF-635, PF-637, PF-638, PF-639, PF-652, PF-643, PF-654, PF-655, PF-656, PF-657, PF-658, PF-659, PF-661, PF-664, PF-667, PF-778, PF-672, PF-677, PF-680, PF-683, PF-685, PF-686, PF-690, PF-692, PF-694, PF-695, PF-738, PF-741, PF-745, PF-746, PF-760, PF-761, PF-763, PF-764, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of S. epidermidis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against of S. epidermidis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-001, PF-003, PF-004, PF-006, PF-007, PF-009, PF-010, PF-012, PF-013, PF-020, PF-021, PF-022, PF-024, PF-025, PF-027, PF-028, PF-030, PF-032, PF-033, PF-034, PF-036, PF-037, PF-040, PF-041, PF-042, PF-043, PF-046, PF-048, PF-051, PF-052, PF-953, PF-956, PF-957, PF-961, PF-963, PF-964, PF-965, PF-967, PF-968, PF-971, PF-073, PF-074, PF-075, PF-076, PF-099, PF-123, PF-124, PF-125, PF-127, PF-128, PF-129, PF-137, PF-139, PF-140, PF-145, PF-148, PF-153, PF-157, PF-171, PF-173, PF-176, PF-178, PF-180, PF-186, PF-190, PF-191, PF-192, PF-196, PF-199, PF-203, PF-204, PF-208, PF-209, PF-226, PF-233, PF-273, PF-278, PF-283, PF-290, PF-292, PF-293, PF-294, PF-296, PF-297, PF-301, PF-307, PF-310, PF-313, PF-318, PF-319, PF-322, PF-335, PF-339, PF-342, PF-347, PF-349, PF-350, PF-355, PF-356, PF-357, PF-360, PF-363, PF-366, PF-369, PF-370, PF-373, PF-374, PF-375, PF-376, PF-378, PF-379, PF-380, PF-381, PF-383, PF-386, PF-387, PF-389, PF-390, PF-393, PF-395, PF-396, PF-397, PF-398, PF-399, PF-401, PF-403, PF-404, PF-406, PF-407, PF-408, PF-410, PF-411, PF-413, PF-417, PF-418, PF-422, PF-425, PF-246, PF-249, PF-430, PF-431, PF-432, PF-439, PF-440, PF-444, PF-447, PF-451, PF-452, PF-453, PF-454, PF-460, PF-469, PF-471, PF-473, PF-474, PF-475, PF-478, PF-480, PF-514, PF-518, PF-526, PF-527, PF-528, PF-530, PF-531, PF-533, PF-534, PF-536, PF-540, PF-543, PF-544, PF-546, PF-547, PF-548, PF-556, PF-558, PF-562, PF-576, PF-577, PF-578, PF-580, PF-583, PF-584, PF-585, PF-586, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-610, PF-612, PF-613, PF-614, PF-615, PF-616, PF-619, PF-622, PF-623, PF-624, PF-627, PF-632, PF-634, PF-635, PF-637, PF-638, PF-655, PF-657, PF-659, PF-664, PF-667, PF-778, PF-672, PF-677, PF-681, PF-683, PF-685, PF-686, PF-690, PF-741, PF-746, PF-760, PF-761, PF-763, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of S. mutans can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against S. mutans in Tables 4, 5, or 6 (e.g., from the group consisting of G-1, G-2, G-4, G-8, PF-020, PF-040, PF-051, PF-531, PF-543, PF-547, PF-578, PF-583, PF-600, PF-606, PF-612, PF-624, PF-634, PF-741, PF-745, PF-746, PF-761, PF-770, PF-776, PF-C005, PF-C057, PF-C058, PF-C061, PF-C062, PF-C072, PF-C075, PF-C084, PF-C085, PF-C088, PF-C098, PF-C131, PF-C135, PF-C139, PF-C142, PF-C146, PF-C180, PF-C194, PF-C281, PF-C290, PF-C291, PF-C293

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of S. pneumoniae can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against S. pneumoniae in Tables 4, 5, or 6 (e.g., from the group consisting of PF-002, PF-005, PF-006, PF-020, PF-033, PF-040, PF-051, PF-053, PF-056, PF-057, PF-061, PF-063, PF-068, PF-071, PF-073, PF-140, PF-144, PF-145, PF-148, PF-171, PF-175, PF-178, PF-220, PF-355, PF-356, PF-357, PF-363, PF-366, PF-380, PF-389, PF-390, PF-393, PF-407, PF-411, PF-414, PF-415, PF-416, PF-417, PF-418, PF-419, PF-421, PF-422, PF-423, PF-424, PF-425, PF-426, PF-427, PF-428, PF-429, PF-430, PF-431, PF-432, PF-433, PF-434, PF-437, PF-439, PF-440, PF-442, PF-443, PF-444, PF-445, PF-446, PF-447, PF-448, PF-449, PF-450, PF-451, PF-452, PF-453, PF-454, PF-455, PF-457, PF-458, PF-469, PF-460, PF-461, PF-462, PF-464, PF-465, PF-466, PF-467, PF-468, PF-469, PF-471, PF-472, PF-473, PF-474, PF-475, PF-476, PF-477, PF-478, PF-479, PF-480, PF-482, PF-485, PF-511, PF-512, PF-513, PF-514, PF-515, PF-516, PF-517, PF-518, PF-519, PF-520, PF-521, PF-522, PF-523, PF-524, PF-525, PF-526, PF-527, PF-528, PF-529, PF-530, PF-531, PF-532, PF-533, PF-534, PF-535, PF-536, PF-537, PF-538, PF-539, PF-540, PF-541, PF-542, PF-543, PF-544, PF-546, PF-548, PF-553, PF-555, PF-556, PF-558, PF-560, PF-562, PF-563, PF-566, PF-567, PF-572, PF-573, PF-575, PF-576, PF-577, PF-578, PF-580, PF-581, PF-583, PF-585, PF-585, PF-586, PF-587, PF-589, PF-591, PF-592, PF-595, PF-596, PF-598, PF-599, PF-600, PF-603, PF-605, PF-606, PF-607, PF-609, PF-610, PF-612, PF-614, PF-615, PF-617, PF-618, PF-619, PF-621, PF-622, PF-623, PF-624, PF-625, PF-626, PF-627, PF-629, PF-631, PF-632, PF-634, PF-635, PF-636, PF-637, PF-638, PF-639, PF-640, PF-643, PF-644, PF-645, PF-646, PF-647, PF-651, PF-652, PF-653, PF-654, PF-655, PF-657, PF-658, PF-659, PF-660, PF-662, PF-663, PF-664, PF-665, PF-666, PF-667, PF-668, PF-670, PF-672, PF-675, PF-677, PF-681, PF-682, PF-683, PF-684, PF-685, PF-686, PF-687, PF-688, PF-690, PF-691, PF-693, PF-694, PF-695, PF-696, PF-697, PF-698, PF-699, PF-700, PF-702, PF-704, PF-737, PF-741, PF-744, PF-745, PF-746, PF-748, PF-749, PF-752, PF-756, PF-757, PF-760, PF-761, PF-762, PF-763, PF-764, PF-770, PF-776, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of A. baumannii can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against A. baumannii in Tables 4, 5, or 6 (e.g., from the group consisting of PF-531, PF-006, PF-538, and PF-530).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of C. jejuni can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against C. jejuni in Tables 4, 5, or 6 (e.g., from the group consisting of PF-006, PF-008, PF-033, PF-040, PF-053, PF-056, PF-057, PF-059, PF-061, PF-063, PF-067, PF-068, PF-069, PF-071, PF-073, PF-140, PF-145, PF-148, PF-171, PF-175, PF-355, PF-356, PF-363, PF-366, PF-380, PF-389, PF-390, PF-392, PF-393, PF-411, PF-418, PF-422, PF-425, PF-426, PF-431, PF-432, PF-456, PF-469, PF-470, PF-471, PF-472, PF-473, PF-474, PF-475, PF-527, PF-548, PF-555, PF-556, PF-558, PF-559, PF-560, PF-562, PF-563, PF-564, PF-566, PF-567, PF-575, PF-576, PF-577, PF-581, PF-584, PF-585, PF-586, PF-590, PF-591, PF-592, PF-595, PF-596, PF-598, PF-599, PF-601, PF-605, PF-607, PF-609, PF-610, PF-614, PF-615, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of E. coli can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against E. coli in Tables 4, 5, or 6 (e.g., from the group consisting of PF-007, PF-040, PF-053, PF-057, PF-068, PF-178, PF-344, PF-347, PF-349, PF-350, PF-355, PF-360, PF-362, PF-363, PF-366, PF-369, PF-370, PF-374, PF-375, PF-376, PF-379, PF-380, PF-381, PF-383, PF-385, PF-386, PF-387, PF-390, PF-395, PF-396, PF-398, PF-399, PF-401, PF-403, PF-410, PF-411, PF-413, PF-418, PF-425, PF-426, PF-427, PF-432, PF-439, PF-440, PF-443, PF-444, PF-451, PF-452, PF-453, PF-454, PF-460, PF-469, PF-471, PF-473, PF-474, PF-478, PF-480, PF-514, PF-518, PF-519, PF-524, PF-526, PF-528, PF-530, PF-531, PF-532, PF-533, PF-534, PF-536, PF-540, PF-541, PF-543, PF-546, PF-576, PF-577, PF-578, PF-584, PF-586, PF-592, PF-595, PF-596, PF-598, PF-600, PF-603, PF-605, PF-606, PF-610, PF-612, PF-615, PF-619, PF-624, PF-634, PF-741, PF-746, PF-761, PF-770, and PF-776).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of F. nucleatum can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against F. nucleatum in Tables 4, 5, or 6 (e.g., from the group consisting of PF-C055, PF-C061, PF-C062, PF-C064, PF-C065, PF-C069, PF-C071, PF-C072, PF-C075, PF-C084, PF-C086, PF-C088, PF-C091, PF-C095, PF-C098, PF-C120, PF-C131, PF-C135, PF-C136, PF-C137, PF-C143, PF-C145, PF-C181, PF-C194, PF-C214, PF-C291, and PF-C293).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of M. Xanthus can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against M. Xanthus in Tables 4, 5, or 6 (e.g., from the group consisting of G-5, G-6, and G-7).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of P. aeruginosa can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against P. aeruginosa in Tables 4, 5, or 6 (e.g., from the group consisting of PF-053, PF-063, PF-067, PF-128, PF-140, PF-143, PF-168, PF-204, PF-209, PF-355, PF-356, PF-366, PF-380, PF-411, PF-425, PF-432, PF-454, PF-458, PF-471, PF-474, PF-527, PF-531, PF-535, PF-536, PF-575, PF-577, PF-605, PF-746, PF-761, and PF-S003).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of P. gingivalis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against P. gingivalis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-C052, PF-C072, PF-C075, PF-C084, PF-C088, PF-C089, PF-C136, PF-C180, PF-C194, and C293).

In certain embodiments a peptide or composition effective to kill or inhibit the growth and/or proliferation of P. mirabilis can comprise one or more peptides and/or one or more peptide domains comprising or consisting of sequences identified as having activity against P. mirabilis in Tables 4, 5, or 6 (e.g., from the group consisting of PF-040, PF-578, PF-612, PF-624, PF-634, PF-741, and PF-770).

It was also a surprising discovery that a number of novel antimicrobial peptides are characterized by the presence of particular amino acid motifs. Such motifs include KIF, FIK, KIH, HIK, and KIV, as illustrated in Table 7.

TABLE 7 Antimicrobial peptides characterized by particular motifs. Omnibus SEQ ID Motif # Sequence NO KIF PF-278 LSLATFA KIF MTRSNWSLKRFNRL 1567 PF-C059 QKIIDMSKFLFSLILFIMIVVIYIGKSIGGYSAIVSS 1568 IMLELDTVLYNK KIF FIYK PF-C073 FE SLLP QATKKIVNNKGSKIN KIF 1569 PF-C085 KKF KIF VIINWFYHKYIILNFEENF 1570 PF-531 YIQFHLNQQPRPKVKKI KIF L 1571 PF-C194 NTNDLLQAFELMGLGMAGVFIVLGILYIVAELLI 1572 KIF PVNN PF-C201 IFKLFEEHLLYLLDAFYYS KIF RRLKQGLYRRKE 1573 QPYTQDLFRM PF-442 MQIFYIKT KIF LSFFLFLLIFSQCFYKIEE 1574 PF-C252 NYRLVNAIFS KIF KKKFIKF 1575 FIK PF-251 MAWK FIK LDKVVSQKECNNFLEKEENKKLLKL 1576 LRIQKNMR PF-261 MDIWK FIK SFNTVNTYLLLSCVLLIILVLYFYVI 1577 NPA PF-497 LVLRICTDLFT FIK WTIKQRKS 1578 PF-775 DLCGQE FIK FKTCVTNQLAKK 1579 PF-591 DLLKSLLGQDGAKNDEIIE FIK IIMEK 1580 PF-597 DEIKVSDEEIEK FIK ENNL 1581 PF-608 LICEVVKPEED FIK VKLNEDNVTAKISREFIAKKI 1582 DA IT-133 Y FIK DDNEALSKDWEVIGNDLKGTIDKYGKEFK 1583 VR PF-C252 NYRLVNAIFSKIFKKK FIK F 1584 PF-C278 DMKIIKLYIKILSFL FIK YCNKKLNSVKLKA 1585 PF-C290 GNVHPESDFHNLIQ FIK TFLYFTIFFKYFL 1586 PF-006 MGIIAGIIK FIK GLIEKFTGK 1587 PF-013 LIQKGLNQTFIVVIRLNN FIK KS 1588 PF-040 MIHLTKQNTMEALH FIK QFYDMFFILNFNV 1589 KIH PF-252 MKKLVAALAVIVILTGCVYDPVNYD KIH DQEF 1590 QDHLRQNG PF-575 LNFRAENKILE KIH ISLIDTVEGSA 1591 PF-533 KTPND KIH KTIIIKHIIL 1592 HIK PF-222 HIK ETR 1593 PF-319 SIGSMIGMYSFRHKTK HIK FTFGIPFILFLQFLLV 1594 YFYILK PF-477 HKNKLNIP HIK S 1595 KIV PF-272 MTLTIKIKHRS KIV PLNLISLVYAFFTYNFVANRI 1596 MFLTND PF-758 PEII KIV SGLL 1597 PF-336 MLTSRKKRLK KIV EEQNKKDESI 1598 PF-C073 FESLLPQATK KIV NNKGSKINKIF 1599 PF-721 TEQAK KIV DILNNWLE 1600 PF-730 FEDIEQIIKYHLIDG KIV APLLLDR 1601 PF-095 KRGS KIV IAIAVVLIVLAGVWVW 1602 PF-028 ALDCSEQSVILWYETILD KIV GVIK 1603 VIK PF-257 VWENRKKYLENEIERHNVFLKLGQE VIK GLNA 1604 LASRGR PF-226 LMFFSENMDKRDTLSGKFRYFAGSK VIK LMNW 1605 LSENGK PF-580 EILNNNQ VIK ELTMKYKTQFESNLGGWTARAR 1606 R PF-366 AL C S VIK AIEL GIINVHL Q 1607 PF-C092 NGDKKAKEELDKWDE VIK ELNIQF 1608 PF-S028 GS VIK KRRKRMSKKKHRKMLRRTRVQRRKLG 1609 K PF-103 VIK ISVPGQVQMLIP 1610 PF-527 GS VIK KRRKRMAKKKHRKLLKKTRIQRRRAGK 1611 PF-167 AIEG VIK KGACFKLLRHEMF 1612 PF-C166 KRKHENVIVAEEMR VIK N 1613 PF-007 MGIIAGIIK VIK SLIEQFTGK 1614 PF-071 HCVIGNVVDIANLLKRRAVYRDIAD VIK MR 1615 PF-028 ALDCSEQSVILWYETILDKIVG VIK 1616 PRP PF-C031 WSESQPPTAT PRP HAEVARAGLVTPPTL 1617 PF-752 LHVIR PRP ELSELKFPITKILKVNKQGLKK 1618 PF-672 MRFGSLALVAYDSAIKHSW PRP SSVRRLRM 1619 PF-088 VMFVLTRGRS PRP MIPAY 1620 PF-143 LS PRP IIVSRRSRADNNNDWSR 1621 PF-168 VLPFPAIPLSRRRACVAA PRP RSRQRAS 1622 PF-531 YIQFHLNQQ PRP KVKKIKIFL 1623 All groups are associated with antimicrobial activity

In certain embodiments, peptides described herein can have multiple activities. Thus for example, a peptide can have both binding/targeting activity and antimicrobial activity. Illustrative peptides having multiple activities are shown in Table 8. Such peptides can be used, e.g., in a chimeric construct, for any or all of these properties. Thus, for example, a peptide designated “B” in Table 8 can be used as a targeting peptide. If it is also designated G or M it can also be used for antimicrobial activity.

TABLE 8 Peptides having multiple activities. B: targeting/binding activity; M: antimicrobial activity; G: Growth or phenotype altering. Peptide Activities PF-001 G B PF-002 G B PF-003 G B PF-004 G B PF-005 G B PF-006 G B M PF-007 G B PF-008 G B PF-009 G B PF-010 G B PF-011 G B PF-012 G B PF-013 G B PF-015 G B PF-017 G B PF-020 G B PF-021 G B PF-022 G B PF-023 G B PF-024 G B PF-025 G B PF-026 G B PF-027 G B PF-028 G B PF-029 G B PF-030 G B PF-031 G B PF-033 G B PF-034 G B PF-035 G B PF-036 G B PF-037 G B PF-040 G B PF-041 G B PF-042 G B PF-043 G B PF-045 G B PF-046 G B PF-048 G B PF-049 G B PF-051 G B PF-052 G B PF-053 G B PF-056 G B PF-057 G B PF-058 G B PF-061 G B PF-063 G B PF-064 G B PF-065 G B PF-066 G B PF-067 G B PF-068 G B PF-069 G B PF-070 G B PF-071 G B PF-073 G B PF-074 G B PF-075 G B PF-076 G B PF-099 G B PF-123 G B PF-124 G B PF-125 G B PF-127 G B PF-128 G B PF-129 G B PF-133 G B PF-135 G B PF-137 G B PF-139 G B PF-140 G B PF-143 G B PF-144 G B PF-145 G B PF-148 G B M PF-149 G B PF-153 G B PF-156 G B PF-157 G B PF-164 G B PF-168 G B M PF-171 G B PF-173 G B PF-175 G B PF-176 G B PF-178 G B PF-180 G B PF-186 G B PF-188 G B PF-190 G B PF-191 G B PF-192 G B PF-196 G B PF-203 G B PF-204 G B PF-208 G B PF-209 G B M PF-212 G B PF-215 G B PF-224 G B PF-226 G B PF-233 G B PF-234 G B PF-235 G B PF-249 G B PF-255 G B PF-257 G B PF-270 G B PF-271 G B PF-273 G B PF-276 G B PF-278 G B M PF-283 G B M PF-289 G B PF-292 G B PF-294 G B PF-297 G B PF-301 G B PF-305 G B PF-306 G B PF-307 G B M PF-313 G B PF-319 G B PF-322 G M PF-344 G B PF-347 G B PF-349 G B PF-350 G B PF-354 G B PF-355 G B PF-356 G B PF-357 G B PF-360 G B PF-362 G B PF-363 G B PF-366 G B PF-369 G B PF-370 G B PF-373 G B PF-374 G B PF-375 G B PF-376 G B PF-378 G B PF-379 G B PF-380 G B PF-381 G B PF-382 G B PF-383 G B PF-385 G B PF-386 G B PF-387 G B PF-389 G B PF-390 G B PF-392 G B PF-393 G B PF-394 G B PF-395 G B PF-396 G B PF-397 G B PF-398 G B PF-399 G B PF-401 G B PF-403 G B PF-404 G B PF-405 G B PF-406 G B PF-407 G B PF-408 G B PF-410 G B PF-411 G B PF-413 G B PF-414 G B PF-416 G B PF-417 G B PF-418 G B PF-421 G B PF-422 G B PF-423 G B PF-424 G B PF-425 G B PF-426 G B PF-427 G B PF-428 G B PF-429 G B PF-430 G B PF-431 G B PF-432 G B PF-433 G B PF-434 G B PF-437 G M PF-439 G B PF-440 G B PF-442 G B PF-443 G B PF-444 G B PF-445 G B PF-446 G B PF-447 G B PF-S003 G B PF-448 G B M PF-450 G B PF-451 G B PF-452 G B PF-453 G B PF-454 G B PF-456 G B PF-457 G B PF-458 G B PF-459 G B PF-460 G B PF-461 G B PF-462 G B PF-464 G B PF-465 G B PF-466 G B PF-467 G B PF-469 G B PF-470 G B PF-471 G B PF-472 G B PF-473 G B PF-474 G B PF-475 G B PF-476 G B PF-477 G B PF-478 G B PF-479 G B PF-480 G B PF-482 G B PF-484 G B PF-497 B M PF-499 B M PF-511 G B M PF-512 G B M PF-513 G B PF-514 G B PF-515 G B PF-516 G PF-517 G B PF-518 G B PF-519 G B PF-520 G B M PF-521 G B M PF-522 G B M PF-523 B M PF-524 G B M PF-525 G M PF-526 G B PF-527 G B M PF-528 G B PF-529 G B M PF-530 G M PF-531 G M PF-537 G B PF-538 G M PF-539 G B PF-540 G B PF-542 G B PF-543 G B PF-544 G B PF-545 G B M PF-546 G B PF-547 G B M PF-548 G B PF-549 G B PF-550 G B PF-551 G B PF-552 G B PF-553 G B PF-554 G B PF-555 G B PF-556 G B PF-557 G B PF-558 G B PF-559 G B PF-560 G B PF-562 G B PF-563 G B PF-564 G B PF-566 G B PF-567 G B PF-569 G B PF-572 G B PF-573 G B PF-575 G B PF-576 G B PF-577 G B PF-578 G B PF-580 G B PF-581 G B PF-583 G B M PF-584 G B PF-585 G B PF-586 G B PF-587 G B PF-588 G B PF-589 G B PF-590 G B PF-592 G B PF-593 G B PF-594 G B PF-595 G B PF-596 G B PF-597 G B PF-598 G B PF-599 G B PF-600 G B M PF-601 G B PF-602 G B PF-603 G B PF-604 G B PF-605 G B PF-606 G M PF-607 G B PF-609 G B PF-610 G B PF-612 G B PF-613 G B PF-614 G B PF-615 G B PF-616 G B PF-617 G B PF-619 G B PF-621 G B PF-622 G B PF-623 G B PF-625 G B PF-626 G B PF-627 G B PF-629 G B PF-630 G B PF-631 G B PF-632 G B PF-634 G B PF-635 G B PF-636 G B PF-637 G B PF-638 G B PF-639 G B PF-640 G B PF-642 G B PF-655 G B PF-664 G B PF-672 G B M PF-681 G B PF-686 G B PF-737 G B PF-738 G B PF-741 G B PF-744 G B PF-745 G B PF-746 G B PF-748 G B PF-749 G B PF-752 G B PF-756 G B PF-757 G B PF-760 G B PF-761 G B PF-762 G B PF-763 G B PF-764 G B PF-770 G B PF-776 G B PF-C052 G B PF-C055 G B PF-C057 G B PF-C058 G B PF-C061 G B PF-C062 G B PF-C064 G B PF-C065 G B PF-C069 G B PF-C071 G B PF-C072 G B PF-C075 G B PF-C084 G B PF-C085 G B PF-C086 G B PF-C088 G B PF-C091 G B PF-C095 G B PF-C098 G B PF-C120 G B PF-C131 G B PF-C135 G B PF-C136 G B PF-C137 G B PF-C139 G B PF-C142 G B PF-C143 G B PF-C145 G B PF-C180 G B PF-C181 G B PF-C194 G B PF-C281 G B PF-C290 G B PF-C291 G B

Other peptides believed to show binding, growth altering, and/or antimicrobial activity are shown in Table 9.

TABLE 9 Additional peptides believed to have binding, growth altering, and/or antimicrobial activity. SEQ ID Sequence ID No. PF-198 RRLASRRSLVVST 1624 PF-227 RLLGLYGENSAAGFIASVIGAVIILFIYNLIARKS 1625 PF-260 GHLRVCWILWLQSANPLSFRHHYLAVMW 1626 PF-261 MDIWKFIKSFNTVNTYLLLSCVLLIILVLYFYVINPA 1627 PF-277 MIIQNKKIEKIYKYQTKEIFLNKTSLRAGFVFRMVRVLI 1628 PF-280 MLIDWQEPDIEKSFCAAFLKISVSVLVYRTPLGYGNQLRE 1629 PF-286 FFDGEVGCGC 1630 PF-287 ILEQNIEEVFFIQS 1631 PF-312 MDKIRIWNNFHISNEYIKQRYGIISIPLFYVYLF 1632 PF-321 FAKKNPCRMRVPNTGTWYLVVNQDGNSGIVNFSINTIQN 1633 PF-327 MLVFQMRYQMRYVDKTSTVLKQTKNSDYADK 1634 PF-330 MLMNFEVYQQRILIIYNKCYHLKAVGKNLQLFIIVD 1635 PF-331 MGRHLWNPSYFVATVSENTEEQIRKYINNQKKQVK 1636 PF-341 DDKNEGKIAQGEY 1637 PF-391 EASVYRE 1638 PF-420 MVKHNFDVTDKTGKISSKHCFEITDKTDVV 1639 PF-708 DRPSQTTHHTLSSSRITGPS 1640 PF-710 EALLPPDPPDEDSQRIIPQ 1641 PF-713 DRPSQTTHHTLSSSRITGPS 1642 PF-715 LEDTKALFPCFVPI 1643 PF-718 KKYSSFKSMIDDLEYDA 1644 PF-719 FKSMIDDLEYDA 1645 PF-721 TEQAKKIVDILNNWLE 1646 PF-722 STSPSVTSVYAEALGLK 1647 PF-723 VGAMAIFLNVVAMLAGV 1648 PF-725 ARTIQNNGCLIHNSRYP 1649 PF-726 CDDLYALEAQGTLNELLKK 1650 PF-729 TPEPVVIVKP 1651 PF-730 FEDIEQIIKYHLIDGKIVAPLLLDR 1652 PF-734 SDIIAEMFQQGELEPMLRDAVAA 1653 PF-736 KGSASGSASGSGSAK 1654 PF-739 KSGASSVASAAKSG 1655 PF-742 AAATTATTAK 1656 PF-743 TKGTTTGTAKTTGVTTGTAK 1657 PF-769 GSRGGAKRGGARG 1658 PF-C031 WSESQPPTATPRPHAEVARAGLVTPPTL 1659 PF-C038 QPIGFPTDSVHGTDLVHRLRGTTSSR 1660 PF-C077 LENLDIEGLTEMKEHIEDLIAEKSAAESIEEVIVEAE 1661 PF-C205 AYSLTFQNPNDNLTDEEVAKYMEKITKALTEKIGAEVR 1662 PF-S016 PLTRETFAERGIRKARVARTFSEEEPPF 1663 III. Design and Construction of STAMPs and Other Chimeric Constructs.

In various embodiments this invention provides chimeric moieties comprising one or more targeting moieties attached to one or more effectors. The targeting moieties can be selected to preferentially bind to a target microorganism (e.g., bacteria, virus, fungi, yeast, alga, protozoan, etc.) or group of microorganisms (e.g., gram-negative or gram-positive bacteria, particular genus, species, etc.) In certain embodiments the targeting moiety comprises one or more novel microorganism-binding peptides as described herein (see, e.g., Table 3, and/or Table 10, and/or Table 12). In certain embodiments the targeting moiety comprises non-peptide moieties (e.g., antibodies, receptor, receptor ligand, lectin, and the like).

In various embodiments the effector comprises a moiety whose activity is to be delivered to the target microorganism(s), to a biofilm comprising the target microorganism(s), to a cell or tissue comprising the target microorganism(s), and the like. In certain embodiments the targeting moiety comprises one or more antimicrobial peptide(s) as described herein (see, e.g., Tables 4, 5 and/or 14), an antibiotic (including, but not limited to a steroid antibiotic), a detectable label, a porphyrin, a photosensitizing agent, an epitope tag, a lipid or liposome, a nanoparticle, a dendrimer, and the like.

In certain embodiments one or more targeting moieties are attached to a single effector. In certain embodiments one or more effectors are attached to a single targeting moiety. In certain embodiments multiple targeting moieties are attached to multiple effectors. The targeting moieties(s) can be attached directly to the effector(s) or through a linker. Where the targeting moiety and the effector comprise peptides the chimeric moiety can be a fusion protein.

A) Targeting Moieties.

In various embodiments this invention provides targeting moieties that preferentially and/or specifically bind to a microorganism (e.g., a bacterium, a fungus, a yeast, etc.). One or more such targeting moieties can be attached to one or more effectors to provide chimeric moieties that are capable of delivering the effector(s) to a target (e.g., a bacterium, a fungus, a yeast, a biofilm comprising the bacterium or fungus or yeast, etc.).

In various embodiments, targeting moieties include, but are not limited to peptides that preferentially bind particular microorganisms (e.g., bacteria, fungi, yeasts, protozoa, algae, viruses, etc.) or groups of such microorganisms, e.g., as described above, antibodies that bind particular microorganisms or groups of microorganisms, receptor ligands that bind particular microorganisms or groups of microorganisms, porphyrins (e.g., metalloporphyrins), lectins that bind particular microorganisms or groups of microorganisms, and the like. As indicated it will be appreciated that references to microorganisms or groups of microorganism include bacteria or groups of bacteria, viruses or groups of viruses, yeasts or groups of yeasts, protozoa or groups of protozoa, viruses or groups of viruses, and the like.

i. Targeting Peptides.

In certain embodiments, the targeting moiety comprises one or more targeting peptides that bind particular bacteria, fungi, and/or yeasts, and/or algae, and/or viruses and/or that bind particular groups of bacteria, and/or groups of fungi, and/or groups of yeasts, and/or groups of algae.

In certain embodiments the targeting peptide can comprise one or more domains capable of binding, specifically binding, or preferentially binding to a microorganism, e.g., a target microbial organism (see, e.g., Table 3). In certain embodiment, the targeting peptide be identified via screening peptide libraries. For example, a phage display peptide library can be screened against a target microbial organism or a desired antigen or epitope thereof. Any peptide identified through such screening can be used as a targeting peptide for the target microbial organism. Illustrative additional targeting peptides are shown in Table 10.

TABLE 10 Additional illustrative targeting moieties. SEQ Targeting Moiety / ID Organism Structure/sequence NO LPSB-1 RGLRRLGRRGLRRLGR 1664 Phob-1 KPVLPVLPVLPVL 1665 LPSB-2 VLRIIRIAVLRIIRIA 1666 LPTG-1 LPETGGSGGSLPETG 1667 α-1 RAHIRRAHIRR 1668 ANION-1 DEDEDDEEDDDEEE 1669 PHILIC-1 STMCGSTMCGSTMCG 1670 SA5.1 / S. aureus VRLPLWLPSLNE 1671 SA5.3 / S. aureus ANYFLPPVLSSS 1672 SA5.4 / S. aureus SHPWNAQRELSV 1673 SA5.5 / S. aureus SVSVGMRPMPRP 1674 SA5.6 / S. aureus WTPLHPSTNRPP 1675 SA5.7 / S. aureus SVSVGMKPSPRP 1676 SA5.8 / S. aureus SVSVGMKPSPRP 1677 SA5.9 / S. aureus SVPVGPYNESQP 1678 SA5.10 / S. aureus WAPPLFRSSLFY 1679 SA2.2 / S. aureus WAPPXPXSSLFY 1680 SA2.4 / S. aureus HHGWTHHWPPPP 1681 SA2.5 / S. aureus SYYSLPPIFHIP 1682 SA2.6 / S. aureus HFQENPLSRGGEL 1683 SA2.7 / S. aureus FSYSPTRAPLNM 1684 SA2.8 / S. aureus SXPXXMKXSXXX 1685 SA2.9 / S. aureus VSRHQSWHPHDL 1686 SA2.10 / S. aureus DYXYRGLPRXET 1687 SA2.11 / S. aureus SVSVGMKPSPRP 1688 S. aureus / Consensus V/Q/H-P/H-H-E-F/Y-K/H-H/A-L/H-X-X-K/R-P/L 1689 DH5.1 / E coli. KHLQNRSTGYET 1690 DH5.2 / E coli. HIHSLSPSKTWP 1691 DH5.3 / E coli. TITPTDAEMPFL 1692 DH5.4 / E coli. HLLESGVLERGM 1693 DH5.5 / E coli. HDRYHIPPLQLH 1694 DH5.6 / E coli. VNTLQNVRHMAA 1695 DH5.7 / E coli. SNYMKLRAVSPF 1696 DH5.8 / E coli. NLQMPYAWRTEF 1697 DH5.9 / E coli. QKPLTGPHFSLI 1698 CSP / S. mutans SGSLSTFFRLFNRSFTQALGK 1699 CSPC18 / S. mutans LSTFFRLFNRSFTQALGK 1700 CSPC16 / S. mutans TFFRLFNRSFTQALGK 1701 CSPM8 / S. mutans TFFRLFNR 1702 KH / Pseudomonas spp KKHRKHRKHRKH 1703 (US 2004/0137482) cCF10 LVTLVFV 1704 AgrD1 YSTCDFIM 1705 AgrD2 GVNACSSLF 1706 AgrD3 YINCDFLL 1707 NisinA ITSISLCTPGCKTGALMGCNMRTATCIICSIIIVSK 1708 PlnA KSSAYSLQMGATAIKQVKKLFKKWGW 1709 S3L1-5 WWYNWWQDW 1710 Penetratin RQIKIWFWNRRMKWKK* 1711 Tat EHWSYCDLRPG 1712 Pep-1N KETWWETWWTEW 1713 Pep27 MRKEFHNVLSSGQLLADKRPARDYNRK 1714 HABP35 LKQKIKHVVKLKVVVKLRSQLVKRKQN 1715 HABP42 (all D) STMMSRSHKTRSHHV 1716 HABP52 GAHWQFNALTVRGGGS 1717 Hi3/17 KQRTSIRATEGCLPS 1718 α-E. coli peptide QEKIRVRLSA 1719 Salivary Receptor QLKTADLPAGRDETTSFVLV* 1720 Adhesion Fragment S1 (Sushi frag.) GFKLKGMARISCLPNGQWSNFPPKCIRECAMVSS 1721 (LPS binding) S3 (Sushi frag.) HAEHKVKIGVEQKYGQFPQGTEVTYTCSGNYFL 1722 (LPS binding) M MArg.1 AMDMYSIEDRYFGGYAPEVG 1723 (Mycoplasma infected cell line binding peptide BPI fragment 1 ASQQGTAALQKELKRIKPDYSDSFKIKH 1724 (LPS binding) 6,376,462 BPI fragment 2 SSQISMVPNVGLKFSISNANIKISGKWKAQKRFL 1725 (LPS binding) K 6,376,462 BPI fragment 3 VHVHISKSKVGWLIQLFHKKIESALRNK 1726 (LPS binding) 6,376,462 LBP fragment 1 AAQEGLLALQSELLRITLPDFTGDLRIPH 1727 (LPS binding) 6,376,462 LBP fragment 2 HSALRPVPGQGLSLSISDSSIRVQGRWKVRKSFF 1728 (LPS binding) K 6,376,462 LBP fragment 3 VEVDMSGDLGWLLNLFHNQIESKFQKV 1729 (LPS binding) 6,376,462 B. anthracis spore ATYPLPIR 1730 binding (WO/1999/036081) Bacillus spore binding peptides of 5-12 amino acids containing the sequence 1731 (WO/1999/036081) Asn-His-Phe-Leu peptides of 5-12 amino acids containing the sequence 1732 Asn-His-Phe-Leu-Pro 1733 Thr-Ser-Glu-Asn-Val-Arg-Thr (TSQNVRT) 1734 A peptide of formula Thr-Tyr-Pro-X-Pro-X-Arg (TYPXPXR) where X is a Ile, Val or Leu. 1735 A peptide having the sequence TSQNVRT. 1736 A peptide having the sequence TYPLPIR LPS binding peptide 1 TFRRLKWK 1737 (6,384,188) LPS BP 2 (6,384,188) RWKVRKSFFKLQ 1738 LPS BP 3 (6,384,188) KWKAQKRFLKMS 1739 Pseudomonas pilin KCTSDQDEQFIPKGCSK 1740 binding peptide (5,494,672) RNAII inhibiting YSPWTNF 1741 peptide (S. Aureus) Patents and patent publications disclosing the referenced antibodies are identified in the table.

In certain embodiments the targeting moieties can comprise other entities, particularly when utilized with an antimicrobial peptide as described, for example, in Table 4. Illustrative targeting moieties can include a polypeptide, a peptide, a small molecule, a ligand, a receptor, an antibody, a protein, or portions thereof that specifically interact with a target microbial organism, e.g., the cell surface appendages such as flagella and pili, and surface exposed proteins, lipids and polysaccharides of a target microbial organism.

ii. Targeting Antibodies.

In certain embodiments the targeting moieties can comprise one or more antibodies that bind specifically or preferentially a microorganism or group of microorganisms (e.g., bacteria, fungi, yeasts, protozoa, viruses, algae, etc.). The antibodies are selected to bind an epitope characteristic or the particular target microorganism(s). In various embodiments such epitopes or antigens are typically is gram-positive or gram-negative specific, or genus-specific, or species-specific, or strain specific and located on the surface of a target microbial organism. The antibody that binds the epitope or antigen can direct an anti-microbial peptide moiety or other effector to the site. Furthermore, in certain embodiments the antibody itself can provide anti-microbial activity in addition to the activity provided by effector moiety since the antibody may engage an immune system effector (e.g., a T-cell) and thereby elicit an antibody-associated immune response, e.g., a humoral immune response.

Antibodies that bind particular target microorganisms can be made using any methods readily available to one skilled in the art. For example, as described in U.S. Pat. No. 6,231,857 (incorporated herein by reference) three monoclonal antibodies, i.e., SWLA1, SWLA2, and SWLA3 have been made against S. mutans. Monoclonal antibodies obtained from non-human animals to be used in a targeting moiety can also be humanized by any means available in the art to decrease their immunogenicity and increase their ability to elicit anti-microbial immune response of a human. Illustrative microorganisms and/or targets to which antibodies may be directed are shown, for example, in Tables 3 and 11.

Various forms of antibody include, without limitation, whole antibodies, antibody fragments (e.g., (Fab′)₂ Fab′, etc.), single chain antibodies (e.g., scFv), minibodies, Di-miniantibody, Tetra-miniantibody, (scFv)₂, Diabody, scDiabody, Triabody, Tetrabody, Tandem diabody, VHH, nanobodies, affibodies, unibodies, and the like.

Methods of making such antibodies are well known to those of skill in the art. In various embodiments, such methods typically involve providing the microorganism, or a component thereof for use as an antigen to raise an immune response in an organism or for use in a screening protocol (e.g., phage or yeast display).

For example, polyclonal antibodies are typically raised by one or more injections (e.g. subcutaneous or intramuscular injections) of the target microorganism(s) or components thereof into a suitable non-human mammal (e.g., mouse, rabbit, rat, etc.).

If desired, the immunizing microorganism or antigen derived therefrom can be administered with or coupled to a carrier protein by conjugation using techniques that are well-known in the art. Such commonly used carriers which are chemically coupled to the peptide include keyhole limpet hemocyanin (KLH), thyroglobulin, bovine serum albumin (BSA), and tetanus toxoid. The coupled peptide is then used to immunize the animal (e.g. a mouse or a rabbit).

The antibodies are then obtained from blood samples taken from the mammal. The techniques used to develop polyclonal antibodies are known in the art (see, e.g., Methods of Enzymology, “Production of Antisera With Small Doses of Immunogen: Multiple Intradermal Injections”, Langone, et al. eds. (Acad. Press, 1981)). Polyclonal antibodies produced by the animals can be further purified, for example, by binding to and elution from a matrix to which the peptide to which the antibodies were raised is bound. Those of skill in the art will know of various techniques common in the immunology arts for purification and/or concentration of polyclonal antibodies, as well as monoclonal antibodies see, for example, Coligan, et al. (1991) Unit 9, Current Protocols in Immunology, Wiley Interscience).

In certain embodiments the antibodies produced will be monoclonal antibodies (“mAb's”). The general method used for production of hybridomas secreting mAbs is well known (Kohler and Milstein (1975) Nature, 256:495

Antibody fragments, e.g. single chain antibodies (scFv or others), can also be produced/selected using phage display and/or yeast display technology. The ability to express antibody fragments on the surface of viruses that infect bacteria (bacteriophage or phage) or yeasts makes it possible to isolate a single binding antibody fragment, e.g., from a library of greater than 10¹⁰ nonbinding clones. To express antibody fragments on the surface of phage (phage display) or yeast, an antibody fragment gene is inserted into the gene encoding a phage surface protein (e.g., pIII) and the antibody fragment-pIII fusion protein is displayed on the phage surface (McCafferty et al. (1990) Nature, 348: 552-554; Hoogenboom et al. (1991) Nucleic Acids Res. 19: 4133-4137).

Since the antibody fragments on the surface of the phage or yeast are functional, phage bearing antigen binding antibody fragments can be separated from non-binding phage by antigen affinity chromatography (McCafferty et al. (1990) Nature, 348: 552-554). Depending on the affinity of the antibody fragment, enrichment factors of 20 fold-1,000,000 fold are obtained for a single round of affinity selection.

Human antibodies can be produced without prior immunization by displaying very large and diverse V-gene repertoires on phage (Marks et al. (1991) J. Mol. Biol. 222: 581-597.

In certain embodiments, nanobodies can be used as targeting moieties. Methods of making V_(h)H (nanobodies) are also well known to those of skill in the art. The Camelidae heavy chain antibodies are found as homodimers of a single heavy chain, dimerized via their constant regions. The variable domains of these camelidae heavy chain antibodies are referred to as V_(HH) domains or V_(HH), and can be either used per se as nanobodies and/or as a starting point for obtaining nanobodies. Isolated V_(HH) retain the ability to bind antigen with high specificity (see, e.g., Hamers-Casterman et al. (1993) Nature 363: 446-448). In certain embodiments such V_(HH) domains, or nucleotide sequences encoding them, can be derived from antibodies raised in Camelidae species, for example in camel, dromedary, llama, alpaca and guanaco. Other species besides Camelidae (e.g. shark, pufferfish) can produce functional antigen-binding heavy chain antibodies, from which (nucleotide sequences encoding) such naturally occurring V_(HH) can be obtained, e.g. using the methods described in U.S. Patent Publication US 2006/0211088.

In various embodiments, for use in therapy, human proteins are preferred, primarily because they are not as likely to provoke an immune response when administered to a patient. Comparisons of camelid V_(HH) with the V_(H) domains of human antibodies reveals several key differences in the framework regions of the camelid V_(HH) domain corresponding to the V_(H)/V_(L) interface of the human V_(H) domains. Mutation of these human residues to V_(HH) resembling residues has been performed to produce “camelized” human V_(H) domains that retain antigen binding activity, yet have improved expression and solubility.

Libraries of single V_(H) domains have also been derived for example from V_(H) genes amplified from genomic DNA or from mRNA from the spleens of immunized mice and expressed in E. coli (Ward et al. (1989) Nature 341: 544-546) and similar approaches can be performed using the V_(H) domains and/or the V_(L) domains described herein. The isolated single VH domains are called “dAbs” or domain antibodies. A “dAb” is an antibody single variable domain (V_(H) or V_(L)) polypeptide that specifically binds antigen. A “dAb” binds antigen independently of other V domains; however, as the term is used herein, a “dAb” can be present in a homo- or heteromultimer with other V_(H) or V_(L) domains where the other domains are not required for antigen binding by the dAb, i.e., where the dAb binds antigen independently of the additional V_(H) or V_(L) domains.

As described in U.S. Patent Publication US 2006/0211088 methods are known for the cloning and direct screening of immunoglobulin sequences (including but not limited to multivalent polypeptides comprising: two or more variable domains—or antigen binding domains—and in particular V_(H) domains or V_(HH) domains; fragments of V_(L), V_(H) or V_(HH) domains, such as CDR regions, for example CDR3 regions; antigen-binding fragments of conventional 4-chain antibodies such as Fab fragments and scFv's, heavy chain antibodies and domain antibodies; and in particular of V_(H) sequences, and more in particular of V_(HH) sequences) that can be used as part of and/or to construct such nanobodies.

Methods and procedures for the production of VHH/nanobodies can also be found for example in WO 94/04678, WO 96/34103, WO 97/49805, WO 97/49805 WO 94/25591, WO 00/43507 WO 01/90190, WO 03/025020, WO 04/062551, WO 04/041863, WO 04/041865, WO 04/041862, WO 04/041867, PCT/BE2004/000159, Hamers-Casterman et al. (1993) Nature 363: 446; Riechmann and Muyldermans (1999) J. Immunological Meth., 231: 25-38; Vu et al. (1997) Molecular Immunology, 34(16-17): 1121-1131; Nguyen et al. (2000) EMBO J., 19(5): 921-930; Arbabi Ghahroudi et al. (19997) FEBS Letters 414: 521-526; van der Linden et al. (2000) J. Immunological Meth., 240: 185-195; Muyldermans (2001) Rev. Molecular Biotechnology 74: 277-302; Nguyen et al. (2001) Adv. Immunol. 79: 261, and the like.

In certain embodiments the antibody targeting moiety is a unibody. Unibodies provide an antibody technology that produces a stable, smaller antibody format with an anticipated longer therapeutic window than certain small antibody formats. In certain embodiments unibodies are produced from IgG4 antibodies by eliminating the hinge region of the antibody. Unlike the full size IgG4 antibody, the half molecule fragment is very stable and is termed a uniBody. Halving the IgG4 molecule left only one area on the UniBody that can bind to a target. Methods of producing unibodies are described in detail in PCT Publication WO2007/059782, which is incorporated herein by reference in its entirety (see, also, Kolfschoten et al. (2007) Science 317: 1554-1557).

Affibody molecules are class of affinity proteins based on a 58-amino acid residue protein domain, derived from one of the IgG-binding domains of staphylococcal protein A. This three helix bundle domain has been used as a scaffold for the construction of combinatorial phagemid libraries, from which Affibody variants that target the desired molecules can be selected using phage display technology (see, e.g., Nord et al. (1997) Nat. Biotechnol. 15: 772-777; Ronmark et al. (2002) Eur. J. Biochem., 269: 2647-2655.). Details of Affibodies and methods of production are known to those of skill (see, e.g., U.S. Pat. No. 5,831,012 which is incorporated herein by reference in its entirety).

It will also be recognized that antibodies can be prepared by any of a number of commercial services (e.g., Berkeley antibody laboratories, Bethyl Laboratories, Anawa, Eurogenetec, etc.).

Illustrative antibodies that bind various microorganisms are shown in Table 11.

TABLE 11 Illustrative antibodies that bind target microorganisms. Source Antibody U.S. Pat. No. 7,195,763 Polyclonal/monoclonal binds specific Gram(+) cell wall repeats U.S. Pat. No. 6,939,543 Antibodies against G(+) LTA U.S. Pat. No. 7,169,903 Antibodies against G(+) peptidoglycan U.S. Pat. No. 6,231,857 Antibody against S. mutans (Shi) U.S. Pat. No. 5,484,591 Gram(−) binding antibodies US 2007/0231321 Diabody binding to Streptococcus surface antigen I/II US 2003/0124635 Antibody against S. mutans US 2006/0127372 Antibodies to Actinomyces naeslundii, Lactobacillus casei US 2003/0092086 Antibody to S. sobrinus U.S. Pat. No. 7,364,738 Monoclonal antibodies to the ClfA protein in S. aureus U.S. Pat. No. 7,632,502 Antibodies against C. albicans U.S. Pat. No. 7,608,265 Monoclonal against C. difficile U.S. Pat. No. 4,777,136 Monoclonal Antibodies against Pseudomonas aeruginosa see, e.g., ab20429, ab20560, Antibody against S. pneumoniae ab79522, ab35165, ab65602 from AbCAMm Cambridge Science Park, U.K.

In addition, antibodies (targeting moieties) that bind other microorganisms can readily be produced using, for example, the methods described above.

iii. Porphyrins.

In certain embodiments porphyrins, or other photosensitizing agents, can be used as targeting moieties in the constructs described herein. In particular, metalloporphyrins, particularly a number of non-iron metalloporphyrins mimic heme in their molecular structure and are actively accumulated by bacteria via high affinity heme-uptake systems. The same uptake systems can be used to deliver antibiotic-porphyrin and antibacterial-porphyrin conjugates. Illustrative targeting porphyrins suitable for this purpose are described in U.S. Pat. No. 6,066,628 and shown herein, for example, in FIGS. 1 and 2.

For example, certain artificial (non-iron) metalloporphyrins (MPs) (Ga-IX, Mn-IX,) are active against Gram-negative and Gram-positive bacteria and acid-fast bacilli (e.g., Y. enterocolitica, N. meningitides, S. marcescens, E. coli, P. mirabills, K. pneumoniae, K. oxytoca, Ps. aeruginosa, C. freundii, E. aerogenes, F. menigosepticum, S. aureus, B. subtilis, S. pyogenes A, E. faecalis, M. smegmatis, M. bovis, M. tuber., S. crevisiae) as described in Tables 1-5 of U.S. Pat. No. 6,066,628. These MPs can be used as targeting moieties against these microorganisms.

Similarly, some MPs are also growth-inhibitory against yeasts, indicating their usefulness targeting moieties to target Candida species (e.g., Candida albicans, C. krusei, C. pillosus, C. glabrata, etc.) and other mycoses including but not limited to those caused by as Trichophyton, Epidermophyton, Histoplasma, Aspergillus, Cryptococcus, and the like.

Porphyrins, and other photosensitizers, also have antimicrobial activity. Accordingly, in certain embodiments, the porphyrins, or other photosensitizers, can be used as effectors (e.g., attached to targeting peptides as described herein). In various embodiments the porphyrins or other photosensitizers can provide a dual functionality, e.g., as a targeting moiety and an antimicrobial and can be attached to a targeting peptide and/or to an antimicrobial peptide as described herein.

Illustrative porphyrins and other photosensitizers are shown in FIGS. 1-11 and described in more detail in the discussion of effectors below.

iv. Pheromones.

In certain embodiments, pheromones from microorganisms can be used as targeting moieties. Illustrative pheromones from bacteria and fungi are shown in Table 12.

TABLE 12 Illustrative bacterial and fungal pheromones utilizable as targeting moieties. Locus tag Product Sequence SEQ ID Bacterial Pheromones gi|1041118|dbj|BAA11198.1| iPD1 [Enterococcus MKQQKKHIAALLF 1742 faecalis] ALILTLVS gi|1113947|gb|AAB35253.1| iAM373sex pheromone SIFTLVA 1743 inhibito [Enterococcus faecalis, Peptide, 7 aa] gi|115412|sp|P13268.1|CAD1_ENTFA Sex pheromone CAD1 LFSLVLAG 1744 gi|116406|sp|P11932.1|CIA_ENTFA Sex pheromone cAM373 AIFILAS 1745 (Clumping-inducing agent)(CIA) gi|117240|sp|P13269.1|CPD1_ENTFA Sex pheromone cPD1 FLVMFLSG 1746 gi|12056953|gb|AAG48144.1| putative peptide DSIRDVSPTFNKIRR 1747 AF322594_1 pheromone PrcA WFDGLFK [Lactobacillus paracasei] gi|123988|sp|P24803.1|IAD1_ENTFA Sex pheromone inhibitor MSKRAMKKIIPLIT 1748 determinant precursor LFVVTLVG (iAD1) gi|126362994|emb|CAM35812.1| precursor of pheromone KDEIYWKPS 1749 peptide ComX [Bacillus amyloliquefaciens FZB42] gi|1587088|prf||2205353A pheromone YSTCDFIM 1750 gi|15900442|ref|NP_345046.1| peptide pheromone B1pC GLWEDLLYNINRY 1751 [Streptococcus AHYIT pneumoniae TIGR4] gi|1617436|emb|CAA66791.1| competence pheromone DIRHRINNSIWRDIF 1752 [Streptococcus gordonii] LKRK gi|1617440|emb|CAA66786.1| competence pheromone DVRSNKIRLWWEN 1753 [Streptococcus gordonii] IFFNKK gi|18307870|gb|AAL67728.1| ComX pheromone PTTREWDG 1754 AF456134_2 precursor [Bacillus mojavensis] gi|18307874|gb|AAL67731.1| ComX pheromone LQIYTNGNWVPS 1755 AF456135_2 precursor [Bacillus mojavensis] gi|29377808|ref|NP_816936.1| sex pheromone inhibitor MSKRAMKKIIPLIT 1756 determinant [Enterococcus LFVVTLVG faecalis V583] gi|3342125|gb|AAC27522.1| putative pheromone GAGKNLIYGMGYG 1757 [Enterococcus faecium] YLRSCNRL gi|41018893|sp|P60242.1|CSP1_ Competence-stimulating EMRLSKFFRDFILQ 1758 STRPN peptide type 1 precursor RKK (CSP-1) gi|57489126|gb|AAW51333.1| PcfP [Enterococcus WSEIEINTKQSN 1759 faecalis] gi|57489152|gb|AAW51349.1| PrgT [Enterococcus HISKERFEAY 1760 faecalis] gi|58616083|ref|YP_195761.1| UvaF [Enterococcus KYKCSWCKRVYTL 1761 faecalis] RKDHRTAR gi|58616111|ref|YP_195802.1| PcfP [Enterococcus WSEIEINTKQSN 1762 faecalis] gi|58616132|ref|YP_195769.1| PrgQ [Enterococcus MKTTLKKLSRYIA 1763 faecalis] VVIAITLIFI gi|58616137|ref|YP_195772.1| PrgT [Enterococcus HISKERFEAY 1764 faecalis] gi|6919848|sp|O33689.1|CSP_ Competence-stimulating DKRLPYFFKHLFSN 1765 STROR peptide precursor (CSP) RTK gi|6919849|sp|O33666.1|CSP2_ Competence-stimulating EMRKPDGALFNLF 1766 STRMT peptide precursor (CSP) RRR gi|6919850|sp|O33668.1|CSP3_ Competence-stimulating EMRKSNNNFFHFL 1767 STRMT peptide precursor (CSP) RRI gi|6919851|sp|O33672.1|CSP1_ Competence-stimulating ESRLPKIRFDFIFPR 1768 STRMT peptide precursor (CSP) KK gi|6919852|sp|O33675.1|CSP4_ Competence-stimulating EIRQTHNIFFNFFKR 1769 STRMT peptide precursor (CSP) R gi|6919853|sp|O33690.1|CSP2_ Competence-stimulating DWRISETIRNLIFPR 1770 STROR peptide precursor (CSP) RK gi|999344|gb|AAB34501.1| cOB1bacterial sex VAVLVLGA 1771 pheromone [Enterococcus faecalis, Peptide, 8 aa] gi|18307878|gb|AAL67734.1| ComX pheromone FFEDDKRKSFI 1772 AF456136_2 precursor [Bacillus subtilis] gi|18307882|gb|AAL67737.1| ComX pheromone FFEDDKRKSFI 1773 AF456137_2 precursor [Bacillus subtilis] gi|28272731|emb|CAD65660.1| accessory gene regulator MKQKMYEAIAHLF 1774 protein D, peptide KYVGAKQLVMCC pheromone precursor VGIWFETKIPDELR [Lactobacillus plantarum K WCFS1] gi|28379890|ref|NP_786782.1| accessory gene regulator MKQKMYEAIAHLF 1775 protein D, peptide KYVGAKQLVMCC pheromone precursor VGIWFETKIPDELR [Lactobacillus plantarum K WCFS1] gi|57489105|gb|AAW51312.1| PrgF [Enterococcus VVAYVITQVGAIRF 1776 faecalis] gi|58616090|ref|YP_195779.1| PrgF [Enterococcus VVAYVITQVGAIRF 1777 faecalis] gi|58616138|ref|YP_195762.1| PrgN [Enterococcus LLKLQDDYLLHLE 1778 faecalis] RHRRTKKIIDEN gi|57489117|gb|AAW51324.1| PcfF [Enterococcus EDIKDLTDKVQSLN 1779 faecalis] ALVQSELNKLIKRK DQS gi|57489119|gb|AAW51326.1| PcfH [Enterococcus WFLDFSDWLSKVP 1780 faecalis] SKLWAE gi|58616102|ref|YP_195792.1| PcfF [Enterococcus EDIKDLTDKVQSLN 1781 faecalis] ALVQSELNKLIKRK DQS gi|58616104|ref|YP_195794.1| PcfH [Enterococcus WFLDFSDWLSKVP 1782 faecalis] SKLWAE Fungi gi|1127585|gb|AAA99765.1| mfa1 gene product MLSIFAQTTQTSAS 1783 EPQQSPTAPQGRDN GSPIGYSSCVVA gi|1127592|gb|AAA99771.1| mfa2 gene product MLSIFETVAAAAPV 1784 TVAETQQASNNEN RGQPGYYCLIA gi|11907715|gb|AAG41298.1| pheromone precursor PSLPSSPPSLLPPLPL 1785 MFalpha1D LKLLATRRPTLVG [Cryptococcus neoformans MTLCV var. neoformans] gi|13810235|emb|CAC37424.1| M-factor precursor Mfm1 MDSMANSVSSSSV 1786 [Schizosaccharomyces VNAGNKPAETLNK pombe] TVKNYTPKVPYMC VIA gi|14269436|gb|AAK58071.1| peptide mating pheromone MDTFTYVDLAAVA 1787 AF378295_1 precursor Bbp2-3 AAAVADEVPRDFE [Schizophyllum DQITDYQSYCIIC commune] gi|14269440|gb|AAK58073.1| peptide mating pheromone SNVHGWCVVA 1788 AF378297_1 precursor Bbp2-1 [Schizophyllum commune] gi|1813600|gb|AAB41859.1| pheromone precursor NTTAHGWCVVA 1789 Bbp1(1) [Schizophyllum commune] gi|24940428|emb|CAD56313.1| a-pheromone MQPSTVTAAPKDK 1790 [Saccharomyces TSAEKKDNYIIKGV paradoxus] FWDPACVIA gi|27549492|gb|AAO17258.1| pheromone phb3.1 GPTWWCVNA 1791 [Coprinopsis cinerea] gi|27549494|gb|AAO17259.1| pheromone phb3.2 SGPTWFCIIQ 1792 [Coprinopsis cinerea] gi|27752314|gb|AAO19469.1| pheromone protein a FTAIFSTLSSSVASK 1793 pecursor [Cryptococcus TDAPRNEEAYSSG neoformans var. grubii] NSP gi|2865510|gb|AACO2682.1| MAT-1 pheromone MFSIFAQPAQTSVS 1794 [Ustilago hordei] ETQESPANHGANP GKSGSGLGYSTCV VA gi|3023372|sp|P78742.1|BB11_ RecName: Full = Mating- NTTAHGWCVVA 1795 SCHCO type pheromone BBP1(1); Flags: Precursor gi|3025079|sp|P56508.1|SNA2_ RecName: Full = Protein SDDNYGSLA 1796 YEAST SNA2 gi|37626077|gb|AAQ96360.1| pheromone precursor Phb3 NGLTFWCVIA 1797 B5 [Coprinopsis cinerea] gi|37626081|gb|AAQ96362.1| pheromone precursor PSWFCVIA 1798 Phb3.2 B45 [Coprinopsis cinerea] gi|37626083|gb|AAQ96363.1| pheromone precursor ASWFCTIA 1799 Phb3.1 B47 [Coprinopsis cinerea] gi|37961432|gb|AAP57503.1| Ste3-like pheromone PHHKIANASDKRR 1800 receptor [Thanatephorus RMYFEIFMCAVL cucumeris] gi|400250|sp|P31962.1|MFA1_ RecName: Full = A1- MLSIFAQTTQTSAS 1801 USTMA specific pheromone; EPQQSPTAPQGRDN AltName: Full = Mating GSPIGYSSCVVA factor A1 gi|400251|sp|P31963.1|MFA2_ RecName: Fu11 = A2- MLSIFETVAAAAPV 1802 USTMA specific pheromone; TVAETQQASNNEN AltName: Full = Mating RGQPGYYCLIA factor A2 gi|41209131|gb|AAR99617.1| lipopeptide mating SLTYAWCVVA 1803 pheromone precursor Bap2(3) [Schizophyllum commune] gi|41209146|gb|AAR99650.1| lipopeptide mating TSMAHAWCVVA 1804 pheromone precursor Bap3(2) [Schizophyllum commune] gi|41209149|gb|AAR99653.1| lipopeptide mating GYCVVA 1805 pheromone precursor Bbp2(8) [Schizophyllum commune] gi|46098187|gb|EAK83420.1| MFA1_USTMA A1- MLSIFAQTTQTSAS 1806 SPECIFIC PHEROMONE EPQQSPTAPQGRDN (MATING FACTOR A1) GSPIGYSSCVVA [Ustilago maydis 521] gi|546861|gb|AAB30833.1| M-factor mating MDSMANTVSSSVV 1807 pheromone NTGNKPSETLNKT [Schizosaccharomyces VKNYTPKVPYMCV pombe] IA gi|5917793|gb|AAD56043.1| pheromone Mfa2 MFSLFETVAAAVK 1808 AF184069_1 [Ustilago hordei] VVSAAEPEHAPTNE GKGEPAPYCIIA gi|6014618|gb|AAF01424.1| Phb3.2.42 [Coprinus LTWFCVIA 1809 AF|86389_1 cinereus] gi|68266363|gb|AAY88882.1| putative pheromone LREKRRRRWFEAF 1810 receptor STE3.4 MGFGL [Coprinellus disseminatus] gi|71012805|ref|XP_758529.1| A1-specific pheromone MLSIFAQTTQTSAS 1811 [Ustilago maydis 521] EPQQSPTAPQGRDN GSPIGYSSCVVA gi|72414834|emb|CAI59748.1| mating factor a1.3 MDALTLFAPVSLG 1812 [Sporisorium reilianum] AVATEQAPVDEER PNRQTFPWIGCVV A gi|72414854|emb|CAI59758.1| mating factor a2.1 MFIFESVVASVQAV 1813 [Sporisorium reilianum] SVAEQDQTPVSEG RGKPAVYCTIA gi|l127587|gb|AAA99767.1| rba1 gene product PWMSLLFSFLALLA 1814 LILPKLSKDDPLGL TRQPR gi|151941959|gb|EDN60315.1| pheromone-regulated ASISLIMEGSANIEA 1815 membrane protein VGKLVWLAAALPL [Saccharomyces cerevisiae AFI YJM789] gi|3025095|sp|Q07549.1|SNA4_ Protein SNA4 ARNVYPSVETPLLQ 1816 YEAST GAAPHDNKQSLVE SPPPYVP gi|73921293|sp|Q08245.3|ZEO1_ RecName: Full = Protein FLKKLNRKIASIFN 1817 YEAST ZEO1; AltName: Ful1 = Zeocin resistance protein 1 gi|74644573|sp|Q9P305.3|IGO2_ RecName: Full = Protein DSISRQGSISSGPPP 1818 YEAST IGO2 RSPNK EDF (E. coli) NNWNN 1819

v. Targeting Enhancers/Opsonins

In certain embodiments compositions are contemplated that incorporate a targeting enhancer (e.g., an opsonin) along with one or more targeting moieties (e.g., targeting peptides). Targeting enhancers include moieties that increase binding affinity, and/or binding specificity, and/or internalization of a moiety by the target cell/microorganism.

Accordingly, in certain embodiments, a targeting moiety and/or a targeted antimicrobial molecule comprise a peptide, with the desired level of binding specificity and/or avidity, attached (e.g., conjugated) to an opsonin. When bound to a target cell through the targeting peptide, the opsonin component encourages phagocytosis and destruction by resident macrophages, dendritic cells, monocytes, or PMNs. Opsonins contemplated for conjugation can be of a direct or indirect type.

Direct opsonins include, fore example, any bacterial surface antigen, PAMP (pathogen-associated molecular pattern), or other molecule recognized by host PRRs (pathogen recognizing receptors). Opsonins can include, but are not limited to, bacterial protein, lipid, nucleic acid, carbohydrate and/or oligosaccharide moieties.

In certain embodiments opsonins include, but are not limited to, N-acetyl-D-glucosamine (GlcNAc), N-acetyl-D-galactosamine (GlaNAc), N-acetylglucosamine-containing muramyl peptides, NAG-muramyl peptides, NAG-NAM, peptidoglycan, teichoic acid, lipoteichoic acid, LPS, o-antigen, mannose, fucose, ManNAc, galactose, maltose, glucose, glucosamine, sucrose, mannosamine, galactose-alpha-1,3-galactosyl-beta-1,4-N-acetyl glucosamine, or alpha-1,3-gal-gal, or other sugars.

In certain embodiments, opsonins include indirect opsonins. Indirect opsonins function through binding to a direct opsonin already present. For example an Fc portion of an antibody, a sugar-binding lectin protein (example MBL), or host complement factors (example C3b, C4b, iC3b).

In certain embodiments the opsonin is to galactose-alpha-1,3-galactosyl-beta-1,4-N-acetyl glucosamine, or alpha-1,3-gal-gal.

Other examples of opsonin molecules include, but are not limited to antibodies (e.g., IgG and IgA), components of the complement system (e.g., C3b, C4b, and iC3b), mannose-binding lectin (MBL) (initiates the formation of C3b), and the like.

Methods of coupling an opsonin to a targeting moiety are well known to those of skill in the art (see, e.g., discussion below regarding attachment of effectors to targeting moieties).

B) Effectors.

Any of a wide number of effectors can be coupled to targeting moieties as described herein to preferentially deliver the effector to a target organism and/or tissue. Illustrative effectors include, but are not limited to detectable labels, small molecule antibiotics, antimicrobial peptides, porphyrins or other photosensitizers, epitope tags/antibodies for use in a pretargeting protocol, agents that physically disrupt the extracellular matrix within a community of microorganisms, microparticles and/or microcapsules, nanoparticles and/or nanocapsules, “carrier” vehicles including, but not limited to lipids, liposomes, dendrimers, cholic acid-based peptide mimics or other peptide mimics, steroid antibiotics, and the like.

i. Detectable Labels.

In certain embodiments chimeric moieties are provided comprising a targeting moiety (e.g., as described in Table 3) attached directly or through a linker to a detectable label. Such chimeric moieties are effective for detecting the presence and/or quantity, and/or location of the microorganism(s) to which the targeting moiety is directed. Similarly these chimeric moieties are useful to identify cells and/or tissues and/or food stuffs and/or other compositions that are infected with the targeted microorganism(s).

Detectable labels suitable for use in such chimeric moieties include any composition detectable by spectroscopic, photochemical, biochemical, immunochemical, electrical, optical, or chemical means. Illustrative useful labels include, but are not limited to, biotin for staining with labeled streptavidin conjugates, avidin or streptavidin for labeling with biotin conjugates fluorescent dyes (e.g., fluorescein, texas red, rhodamine, green fluorescent protein, and the like, see, e.g., Molecular Probes, Eugene, Oreg., USA), radiolabels (e.g., ³H, ¹²⁵I, ³⁵S, ¹⁴C, ³²P, ⁹⁹Tc, ²⁰³Pb, ⁶⁷GA, ⁶⁸Ga, ⁷²As, ¹¹¹In, ^(113m)In, ⁹⁷Ru, ⁶²Cu, 641Cu, ⁵²Fe, ^(52m)Mn, ⁵¹Cr, ¹⁸⁶Re, ¹⁸⁸Re, ⁷⁷As, ⁹⁰Y, ⁶⁷Cu, ¹⁶⁹Er, ¹²¹Sn, ¹²⁷Te, ¹⁴²Pr, ¹⁴³Pr, ¹⁹⁸Au, ¹⁹⁹Au, ¹⁶¹Tb, ¹⁰⁹Pd, ¹⁶⁵Dy, ¹⁴⁹Pm, ¹⁵¹Pm, ¹⁵³Sm, ¹⁵⁷Gd, ¹⁵⁹Gd, ¹⁶⁶Ho, ¹⁷²Tm, ¹⁶⁹Yb, ¹⁷⁵Yb, ¹⁷⁷Lu, ¹⁰⁵Ru, ¹¹¹Ag, and the like), enzymes (e.g., horse radish peroxidase, alkaline phosphatase and others commonly used in an ELISA), various colorimetric labels, magnetic or paramagnetic labels (e.g., magnetic and/or paramagnetic nanoparticles), spin labels, radio-opaque labels, and the like. Patents teaching the use of such labels include, for example, U.S. Pat. Nos. 3,817,837; 3,850,752; 3,939,350; 3,996,345; 4,277,437; 4,275,149; and 4,366,241.

It will be recognized that fluorescent labels are not to be limited to single species organic molecules, but include inorganic molecules, multi-molecular mixtures of organic and/or inorganic molecules, crystals, heteropolymers, and the like. Thus, for example, CdSe—CdS core-shell nanocrystals enclosed in a silica shell can be easily derivatized for coupling to a biological molecule (Bruchez et al. (1998) Science, 281: 2013-2016). Similarly, highly fluorescent quantum dots (zinc sulfide-capped cadmium selenide) have been covalently coupled to biomolecules for use in ultrasensitive biological detection (Warren and Nie (1998) Science, 281: 2016-2018).

In various embodiments spin labels are provided by reporter molecules with an unpaired electron spin which can be detected by electron spin resonance (ESR) spectroscopy. Illustrative spin labels include organic free radicals, transitional metal complexes, particularly vanadium, copper, iron, and manganese, and the like. Exemplary spin labels include, for example, nitroxide free radicals.

Means of detecting such labels are well known to those of skill in the art. Thus, for example, where the label is a radioactive label, means for detection include a scintillation counter or photographic film as in autoradiography. Where the label is a fluorescent label, it may be detected by exciting the fluorochrome with the appropriate wavelength of light and detecting the resulting fluorescence, e.g., by microscopy, visual inspection, via photographic film, by the use of electronic detectors such as charge coupled devices (CCDs) or photomultipliers and the like. Similarly, enzymatic labels may be detected by providing appropriate substrates for the enzyme and detecting the resulting reaction product. Finally, simple colorimetric labels may be detected simply by observing the color associated with the label.

ii. Antibiotics.

In certain embodiments chimeric moieties are provided comprising a targeting moiety (e.g. as described in Table 3) attached directly or through a linker to a small molecule antibiotic and/or to a carrier (e.g., a lipid or liposome, a polymer, etc.) comprising a small molecule antibiotic. Illustrative antibiotics are shown in Table 13.

TABLE 13 Illustrative antibiotics for use in the chimeric moieties described herein. Class Generic Name BRAND NAME Aminoglycosides Amikacin AMIKIN® Gentamicin GARAMYCIN® Kanamycin KANTREX® Neomycin Netilmicin NETROMYCIN® Streptomycin Tobramycin NEBCIN® Paromomycin HUMATIN® Carbacephem Loracarbef LORABID® Carbapenems Ertapenem INVANZ® Doripenem FINIBAX® Imipenem/Cilastatin PRIMAXIN® Meropenem MERREM® Cephalosporins (First generation) Cefadroxil DURICEF® Cefazolin ANCEF® Cefalotin or Cefalothin KEFLIN® Cefalexin KEFLEX® Cephalosporins (Second generation) Cefaclor CECLOR® Cefamandole MANDOLE® Cefoxitin MEFOXIN® Cefprozil CEFZIL® Cefuroxime CEFTIN, ZINNAT® Cephalosporins (Third generation) Cefixime SUPRAX® Cefdinir OMNICEF® Cefditoren SPECTRACEF® Cefoperazone CEFOBID® Cefotaxime CLAFORAN® Cefpodoxime Ceftazidime FORTAZ® Ceftibuten CEDAX® Ceftizoxime Ceftriaxone ROCEPHIN® Cephalosporins (Fourth generation) Cefepime MAXIPIME® Cephalosporins (Fifth generation) Ceftobiprole Glycopeptides Teicoplanin Vancomycin VANCOCIN® Macrolides Azithromycin Zithromax Clarithromycin Biaxin Dirithromycin Erythromycin Erythocin, Erythroped Roxithromycin Troleandomycin Telithromycin Ketek Monobactams Aztreonam Penicillins Amoxicillin NOVAMOX®, AMOXIL® Ampicillin Azlocillin Carbenicillin Cloxacillin Dicloxacillin Flucloxacillin FLOXAPEN® Mezlocillin Meticillin Nafcillin Oxacillin Penicillin Piperacillin Ticarcillin Polypeptides Bacitracin Colistin Polymyxin B Quinolones Mafenide Prontosil (archaic) Sulfacetamide Sulfamethizole Sulfanilimide (archaic) Sulfasalazine Sulfisoxazole Trimethoprim BACTRIM® Trimethoprim- Sulfamethoxazole (Co- trimoxazole) (TMP-SMX) Tetracyclines Demeclocycline Doxycycline VIBRAMYCIN® Minocycline MINOCIN® Oxytetracycline TERRACIN® Tetracycline SUMYCIN® Natural products Antimicrobial herbal extracts Essential oils Farnesol Licorice root extracts Glycyrrhizol A Glycyrrhizol B 6,8-diisopreny1-5,7,4′- trihydroxyisoflavone Others Arsphenamine SALVARSANO Chloramphenicol CHLOROMYCETIN® Clindamycin CLEOCIN® Lincomycin Ethambutol Fosfomycin Fusidic acid FUCIDIN® Furazolidone Isoniazid Linezolid ZYVOX® Metronidazole FLAGYL® Mupirocin BACTROBAN® Nitrofurantoin MACRODANTIN®, MACROBID® Platensimycin Pyrazinamide Quinupristin/Dalfopristin SYNCERCID® Rifampin or Rifampicin Tinidazole Artemisinin Antifungals Amphotericin B Anidulafungin Caspofungin acetate Clotrimazole Fluconazole Flucytosine Griseofulvin Itraconazole Ketoconazole Micafungin Miconazole Nystatin Pentamidine Posaconazole Terbinafine Voriconazole Antimycobiotics Aminosalicylic Acid Capreomycin Clofazimine Cycloserine Ethionamide Rifabutin Rifapentine Antivirals Abacavir Acyclovir Adefovir Amantadine Atazanavir Cidofovir Darunavir Didanosine Docosanol Efavirenz Emtricitabine Enfuvirtide Entecavir Etravirine Famciclovir Fomivirsen Fosamprenavir Foscarnet Ganciclovir Idoxuridine Indinavir Interferon alpha Lamivudine Lopinavir/ritonavir Maraviroc Nelfinavir Nevirapine Oseltamivir Penciclovir Peramivir Raltegravir Ribavirin Rimantadine Ritonavir Saquinavir Stavudine Telbivudine Tenofovir Tipranavir Trifluridine Valacyclovir Valganciclovir Zanamivir Zidovudine Anti-parasitics Albendazole Artesunate Atovaquone Bephenium hydroxynaphthoate Chloroquine Dapsone Diethyl-carbamazine Diloxanide furoate Eflornithine Emetine HCl Furazolidone Ivermectin Lindane Mebendazole Mefloquine Melarsoprol Miltefosine Niclosamide Nifurtimox Nitazoxanide Oxamniquine Paromomycin Permethrin Piperazine Praziquantel Primaquine Pyrantel pamoate Pyrimethamine Proguanil Quinacrine HCl Quinidine Quinine Sodium Stibogluconate Spiramycin Thiabendazole Tinidazole

iii. Porphyrins and Non-Porphyrin Photosensitizers.

In certain embodiments, porphyrins and other photosensitizers can be used as targeting moieties and/or as effectors in the methods and compositions of this invention. A photosensitizer is a drug or other chemical that increases photosensitivity of the organism (e.g., bacterium, yeast, fungus, etc.). As targeting moieties the photosensitizers (e.g., porphyrins) are preferentially uptaken by the target microorganisms and thereby facilitate delivery of the chimeric moiety to the target microorganism.

As effectors, photosensitizers can be useful in photodynamic antimicrobial chemotherapy (PACT). In various embodiments PACT utilizes photosensitizers and light (e.g., visible, ultraviolet, infrared, etc.) in order to give a phototoxic response in the target organism(s), often via oxidative damage.

Currently, the major use of PACT is in the disinfection of blood products, particularly for viral inactivation, although more clinically-based protocols are used, e.g. in the treatment of oral infection or topical infection. The technique has been shown to be effective in vitro against bacteria (including drug-resistant strains), yeasts, viruses, parasites, and the like.

Attaching a targeting moiety (e.g., a targeting peptide) to the photosensitizer, e.g., as described herein, provides a means of specifically or preferentially targeting the photosensitizer(s) to particular species or strains(s) of microorganism.

A wide range of photosensitizers, both natural and synthetic are known to those of skill in the art (see, e.g., Wainwright (1998) J. Antimicrob. Chemotherap. 42: 13-28). Photosensitizers are available with differing physicochemical make-up and light-absorption properties. In various embodiments photosensitizers are usually aromatic molecules that are efficient in the formation of long-lived triplet excited states. In terms of the energy absorbed by the aromatic-system, this again depends on the molecular structure involved. For example: furocoumarin photosensitizers (psoralens) absorb relatively high energy ultraviolet (UV) light (c. 300-350 nm), whereas macrocyclic, heteroaromatic molecules such as the phthalocyanines absorb lower energy, near-infrared light.

Illustrative photosensitizers include, but are not limited to porphyrinic macrocyles (especially porphyrins, chlorines, etc., see, e.g., FIGS. 1 and 2). In particular, metalloporphyrins, particularly a number of non-iron metalloporphyrins mimic haem in their molecular structure and are actively accumulated by bacteria via high affinity haem-uptake systems. The same uptake systems can be used to deliver antibiotic-porphyrin and antibacterial-porphyrin conjugates. Illustrative targeting porphyrins suitable for this purpose are described in U.S. Pat. No. 6,066,628 and shown herein in FIGS. 1 and 2.

Illustrative examples of targeted porphyrins are described in Example 5 and associated figures and in FIG. 13.

For example, certain artificial (non-iron) metalloporphyrins (MPs) (Ga-IX, Mn-IX,) are active against Gram-negative and Gram-positive bacteria and acid-fast bacilli (e.g., Y. enterocolitica, N. meningitides, S. marcescens, E. coli, P. mirabills, K. pneumoniae, K. oxytoca, Ps. aeruginosa, C. freundii, E. aerogenes, F. menigosepticum, S. aureus, B. subtilis, S. pyogenes A, E. faecalis, M smegmatis, M. bovis, M. tuber., S. crevisiae) as described in Tables 1-5 of U.S. Pat. No. 6,066,628. These MPs can be used as targeting moieties against these microorganisms.

Similarly, some MPs are also growth-inhibitory against yeasts, indicating their usefulness targeting moieties to target Candida species (e.g., Candida albicans, C. krusei, C. pillosus, C. glabrata, etc.) and other mycoses including but not limited to those caused by as Trichophyton, Epidermophyton, Histoplasma, Aspergillus, Cryptococcus, and the like.

Other photosensitizers include, but are not limited to cyanines (see, e.g., FIG. 6) and phthalocyanines (see, e.g., FIG. 4), azines (see, e.g., FIG. 5) including especially methylene blue and touidine blue, hypericin (see, e.g., FIG. 8), acridines (see, e.g., FIG. 9) including especially Rose Bengal (see, e.g., FIG. 10), crown ethers (see, e.g., FIG. 11), and the like. In certain embodiments, the photosensitizers include tin chlorin 6 and related compounds (e.g., other chlorines and tin porphyrins).

Another light-activated compound is cucumin (see, FIG. 12).

In certain embodiments the photosensitizers are toxic or growth inhibitors without light activation. For example, some non-iron metalloporphyrins (MPs) (see, e.g., FIGS. 1 and 2 herein) possess a powerful light-independent antimicrobial activity. In addition, haemin, the most well known natural porphyrin, possesses a significant antibacterial activity that can augmented by the presence of physiological concentrations of hydrogen peroxide or a reducing agent.

Typically, when activated by light, the toxicity or growth inhibition effect is substantially increased. Typically, they generate radical species that affect anything within proximity. In certain embodiments to get the best selectivity from targeted photosensitizers, anti-oxidants can be used to quench un-bound photosensitizers, limiting the damage only to cells where the conjugates have accumulated due to the targeting peptide. The membrane structures of the target cell act as the proton donors in this case.

In typical photodynamic antimicrobial chemotherapy (PACT) the targeted photosensitizer is “activated by the application of a light source (e.g., a visible light source, an ultraviolet light source, an infrared light source, etc.). PACT applications however need not be limited to topical use. Regions of the mouth, throat, nose, sinuses are readily illuminated. Similarly regions of the gut can readily be illuminated using endoscopic techniques. Other internal regions can be illumined using laparoscopic methods or during other surgical procedures. For example, in certain embodiments involving the insertion or repair or replacement of an implantable device (e.g., a prosthetic device) it contemplated that the device can be coated or otherwise contacted with a chimeric moiety comprising a targeting moiety attached to a photosensitizer as described herein. During the surgical procedure and/or just before closing, the device can be illuminated with an appropriate light source to activate the photosensitizer.

The targeted photosensitizers and uses thereof described herein are illustrative and not to be limiting. Using the teachings provided herein, other targeted photosensitizers and uses thereof will be available to one of skill in the art.

iv. Antimicrobial Peptides.

In certain embodiments, the effector can comprise one or more antimicrobial peptides or compound antimicrobial peptides, e.g., as described above. Numerous antimicrobial peptides are well known to those of skill in the art.

In certain embodiments the antimicrobial peptides comprise one or more amino acid sequences described above (e.g., one or more domains comprising amino acid sequences in Tables 4 and/or 5) and/or one or more of the amino acid sequences shown in Table 14. In certain embodiments the antimicrobial peptides comprise one or more amino acid sequences described in the “Collection of Anti-Microbial Peptides” (CAMP) an online database developed for advancement the understanding of antimicrobial peptides (see, e.g., Thomas et al. (2009) Nucleic Acids Research, 2009, 1-7.doi:10.1093/nar/gkp1021) available at www.bicnirrh.res.in/antimicrobial.

TABLE 14 Other illustrative antimicrobial peptides. AP numbers refer to ID in antimicrobial peptide database (http://aps.unmc.edu/AP/main.php). SEQ ID Effector Structure/Sequence No AP00274 1BH4, Circulin A GIPCGESCVWIPCISAALGCSCKNK 1820 (CirA, plant VCYRN cyclotides, XXC, ZZHp) AP00036 1BNB, Beta- DFASCHTNGGICLPNRCPGHMIQIG 1821 defensin 1 (cow) ICFRPRVKCCRSW AP00047 1BNB, Bovine GPLSCGRNGGVCIPIRCPVPMRQIG 1822 neutrophil beta- TCFGRPVKCCRSW defensin 12 (BNBD-12, cow) AP00428 1C01, MiAMP1 SAFTVWSGPGCNNRAERYSKCGCS 1823 (Macadamia AIHQKGGYDFSYTGQTAALYNQA integrifolia GCSGVAHTRFGSSARACNPFGWKS antimicrobial IFIQC peptide 1, plant) AP00154 1CIX, Tachystatin YSRCQLQGFNCVVRSYGLPTIPCC 1824 A2 (Horseshoe RGLTCRSYFPGSTYGRCQRY crabs, Crustacea, BBS) AP00145 1CW5, VNYGNGVSCSKTKCSVNWGQAFQ 1825 Carnobacteriocin ERYTAGINSFVSGVASGAGSIGRRP B2 (CnbB2, class HA bacteriocin,bacteria) AP00153 1CZ6, Androctonin RSVCRQIKICRRRGGCYYKCTNRP 1826 (scorpions) Y AP00152 1D6X, Tritrpticin VRRFPWWWPFLRR 1827 (synthetic) AP00201 1D7N, Mastoparan INLKALAALAKKIL 1828 (insect) AP00140 1D9J, CecropinA- KWKLFKKIGIGKFLHSAKKF 1829 Magainin2 hybrid (synthetic) AP00178 1DFN, human DCYCRIPACIAGERRYGTCIYQGRL 1830 alpha Defensin WAFCC HNP-3 (human neutrophil peptide- 3, HNP3, human defensin, ZZHh) AP01153 1DQC, Tachycitin YLAFRCGRYSPCLDDGPNVNLYSC 1831 (horseshoe crabs, CSFYNCHKCLARLENCPKGLHYN Crustacea, BBS) AYLKVCDWPSKAGCT AP00437 1DUM, Magainin 2 GIGKYLHSAKKFGKAWVGEIMNS 1832 analog (synthetic) AP00451 1E4S, Human beta DHYNCVSSGGQCLYSACPIFTKIQG 1833 defensin 1 (HBD-1,  TCYRGKAKCCK human defensin) AP00149 1EWS, Rabbit MPCSCKKYCDPWEVIDGSCGLFNS 1834 kidney defensin 1 KYICCREK (RK-1) AP00141 1F0E, CecropinA- KWKLFKKIPKFLHSAKKF 1835 Magainin2 Hybrid (P18, synthetic) AP00142 1F0G, CecropinA- KLKLFKKIGIGKFLHSAKKF 1836 Magainin2 Hybrid (synthetic) AP00143 1F0H, CecropinA- KAKLFKKIGIGKFLHSAKKF 1837 Magainin2 Hybrid (synthetic) AP00524 1FD4, Human beta GIGDPVTCLKSGAICHPVFCPRRYK 1838 defensin 2 (HBD-2,  QIGTCGLPGTKCCKKP human defensin, ZZHh) AP00438 1FJN, Mussel GFGCPNNYQCHRHCKSIPGRCGGY 1839 Defensin MGD-1 CGGWHRLPCTCYRCG AP00155 1FRY, SMAP-29 RGLRRLGRKIAHGVKKYGPTVLRII 1840 (SMAP29, sheep RIAG cathelicidin) AP00150 1G89, Indolicidin ILPWKWPWWPWRR 1841 (cow cathelicidin, BBN, ZZHa) AP00156 1GR4, Microcin VGIGTPISFYGGGAGHVPEYF 1842 J25, linear (MccJ25, bacteriocin, bacteria) AP00151 1HR1, Indolicidin ILAWKWAWWAWRR 1843 P to A mutant (synthetic) AP00196 1HU5, Ovispirin-1 KNLRRIIRKIIHIIKKYG 1844 (synthetic) AP00197 1HU6, Novispirin KNLRRIIRKGIHIIKKYG 1845 G10 (synthetic) AP00198 1HU7, Novispirin KNLRRITRKIIHIIKKYG 1846 T7 (synthetic) AP00445 1HVZ, Monkey GFCRCLCRRGVCRCICTR 1847 RTD-1 (rhesus theta-defensin-1, minidefensin-1, animal defensin, XXC, BBS, lectin, ZZHa) AP00103 1i2v, Heliomicin DKLIGSCVWGAVNYTSDCNGECL 1848 variant (Hel-LL, LRGYKGGHCGSFANVNCWCET synthetic) AP00216 1ICA, Phormia ATCDLLSGTGINHSACAAHCLLRG 1849 defensin A ( insect  NRGGYCNGKGVCVCRN defensin A) AP01224 1Jo3, Gramicidin B VGALAVVVWLFLWLW 1850 (bacteria) AP01225 1jo4, Gramicidin C VGALAVVVWLYLWLW 1851 (bacteria) AP00191 1KFP, Gomesin ECRRLCYKQRCVTYCRGR 1852 (Gm, Spider, XXA) AP00283 1KJ6, Huamn beta GIINTLQKYYCRVRGGRCAVLSCL 1853 defensin 3 (HBD-3, PKEEQIGKCSTRGRKCCRRKK human defensin, ZZHh) AP00147 1KV4, Moricin AKIPIKAIKTVGKAVGKGLRAINIA 1854 (insect, silk moth)  STANDVFNFLKPKKRKA AP00227 1L4V, Sapecin ATCDLLSGTGINHSACAAHCLLRG 1855 (insect, flesh fly)  NRGGYCNGKAVCVCRN AP01161 1L9L, Human GRDYRTCLTIVQKLKKMVDKPTQ 1856 granulysin RSVSNAATRVCTRGRSRWRDVCR (huGran) NFMRRYQSRVIQGLVAGETAQQIC EDLRLCIPSTGPL AP00026 1LFC, FKCRRWQWRMKKLGAPSITCVRR 1857 Lactoferricin_B AF (LfcinB, cow, ZZHa) AP00193 1M4F, human DTHFPICIFCCGCCHRSKCGMCCKT 1858 LEAP-1 (Hepcidin 25) AP00499 1MAG, Gramicidin VGALAVVVWLWLWLW 1859 A (gA, bacteria) AP00403 1MM0, Termicin ACNFQSCWATCQAQHSIYFRRAFC 1860 (termite defensin,  DRSQCKCVFVRG insect defensin) AP00194 1MMC, Ac-AMP2 VGECVRGRCPSGMCCSQFGYCGK 1861 (plant defensin, GPKYCGR BBS) AP01206 1MQZ, Mersacidin CTFTLPGGGGVCTLTSECIC 1862 (bacteria) AP00429 1NKL, Porcine GYFCESCRKIIQKLEDMVGPQPNE 1863 NK-Lysin (pig) DTVTQAASQVCDKLKILRGLCKKI MRSFLRRISWDILTGKKPQAICVDI KICKE AP00633 1og7, Sakacin P/ KYYGNGVHCGKHSCTVDWGTAIG 1864 Sakacin 674 (SakP,  NIGNNAAANWATGGNAGWNK class HA bacteriocin, bacteria) AP00195 1PG1, Protegrin 1 RGGRLCYCRRRFCVCVGR 1865 (Protegrin-1, PG-1, pig cathelicidin, XXA, ZZHa, BBBm) AP00928 1PXQ, Subtilosin NKGCATCSIGAACLVDGPIPDFEIA 1866 A (XXC, class I GATGLFGLWG bacteriocin, Gram- positive bacteria) AP00480 1Q71, Microcin VGIGTPIFSYGGGAGHVPEYF 1867 J25 (cyclic MccJ25, class I microcins, bacteriocins, Gram- negative bacteria, XXC; BBP) AP00211 1RKK, RRWCFRVCYRGFCYRKCR 1868 Polyphemusin I (crabs, Crustacea) AP00430 1T51, IsCT ILGKIWEGIKSLF 1869 (Scorpion) AP00731 1ut3, Spheniscin-2 SFGLCRLRRGFCARGRCRFPSIPIGR 1870 (Sphe-2, penguin CSRFVQCCRRVW defensin, avian defensin) AP00013 1VM5, Aurein 1.2 GLFDIIKKIAESF 1871 (frog) AP00214 1WO1, KWCFRVCYRGICYRRCR 1872 Tachyplesin I (crabs, Crustacea, XXA, ZZHa) AP00644 1xc0, Pardaxin 4 GFFALIPKIISSPLFKTLLSAVGSALS 1873 (Pardaxin P-4, SSGGQE Pardaxin P4, Pa4, flat fish) AP00493 1XKM, Distinctin NLVSGLIEARKYLEQLHRKLKNCK 1874 (two chains for V stability and transport? frog) AP00420 1XV3, Penaeidin- HSSGYTRPLRKPSRPIFIRPIGCDVC 1875 4d (penaeidin 4, YGIPSSTARLCCFRYGDCCHL shrimp, Crustacea) AP00035 1YTR, Plantaricin KSSAYSLQMGATAIKQVKKLFKK 1876 A (PlnA, WGW bacteriocin, bacteria) AP00166 1Z64, Pleurocidin GWGSFFKKAAHVGKHVGKAALT 1877 (fish) HYL AP00780 1Z6V, Human GRRRRSVQWCAVSQPEATKCFQW 1878 lactoferricin QRNMRKVRGPPVSCIKRDSPIQCIQ A AP00549 1ZFU, Plectasin GFGCNGPWDEDDMQCHNHCKSIK 1879 (fungi, fungal GYKGGYCAKGGFVCKCY defensin) AP00177 1ZMH, human CYCRIPACIAGERRYGTCIYQGRL 1880 alpha Defensin WAFCC HNP-2 (human neutrophil peptide- 2, HNP2, human defensin, ZZHh) AP00179 1ZMM, human VCSCRLVFCRRTELRVGNCLIGGV 1881 alpha Defensin SFTYCCTRVD HNP-4 (human neutrophil peptide- 4, HNP4, human defensin) AP00180 1ZMP, human QARATCYCRTGRCATRESLSGVCE 1882 alpha Defensin ISGRLYRLCCR HD-5 (HD5, human defensin) AP00181 1ZMQ, human STRAFTCHCRRSCYSTEYSYGTCT 1883 alpha Defensin VMGINHRFCCL HD-6 (HD6, human defensin) AP00399 1ZRW, Spinigerin HVDKKVADKVLLLKQLRIMRLLT 1884 (insect, termite)  RL AP01157 1ZRX, Stomoxyn RGFRKHFNKLVKKVKHTISETAHV 1885 (insect) AKDTAVIAGSGAAVVAAT AP00637 2A2B, Curvacin_A / ARSYGNGVYCNNKKCWVNRGEA 1886 sakacin_A (CurA,  TQSIIGGMISGWASGLAGM SakA, class IIA bacteriocin, bacteria) AP00558 2B68, Cg-Def GFGCPGNQLKCNNHCKSISCRAGY 1887 (Crassostrea gigas  CDAATLWLRCTCTDCNGKK defensin, oyster defensin, animal defensin) AP01154 2B9K, LCI AIKLVQSPNGNFAASFVLDGTKWI 1888 (bacteria) FKSKYYDSSKGYWVGIYEVWDRK AP01005 2DCV, Tachystatin YVSCLFRGARCRVYSGRSCCFGYY 1889 B1 (BBS, CRRDFPGSIFGTCSRRNF horseshoe crabs) AP01006 2DCW, YITCLFRGARCRVYSGRSCCFGYY 1890 Tachystatin B1 CRRDFPGSIFGTCSRRNF (BBS, horseshoe crabs) AP00275 2ERI, Circulin B CGESCVFIPCISTLLGCSCKNKVCY 1891 (CirB, plant RNGVIP cyclotides, XXC, ZZHp) AP00707 2f3a, LLAA (LL- RLFDKIRQVIRKF 1892 37-derived aurein 1.2 analog, retro- FK13, synthetic) AP00708 2fbs, FK-13 (FK13, FKRIVQRIKDFLR 1893 NMR-discovered LL-37 core peptide, XXA, ZZHs, synthetic) AP00088 2G9L, Gaegurin-4 GILDTLKQFAKGVGKDLVKGAAQ 1894 (Gaegurin 4, frog)  GVLSTVSCKLAKTC AP01011 2G9P, Latarcin 2a GLFGKLIKKFGRKAISYAVKKARG 1895 (Ltc2a, BBM, KH spider) AP00612 2GDL, Fowlicidin- LVQRGRFGRFLRKIRRFRPKVTITI 1896 2 (chCATH-2, bird QGSARFG cathelicidin, chicken cathelicidin, BBL) AP00402 2GL1, VrD2 KTCENLANTYRGPCFTTGSCDDHC 1897 (Vigna radiata KNKEHLRSGRCRDDFRCWCTRNC defensin 2, plant defensin, mung bean) AP00285 2GW9, Cryptdin-4 GLLCYCRKGHCKRGERVRGTCGIR 1898 (Crp4, animal FLYCCPRR defensin, alpha, mouse) AP00613 2hfr, Fowlicidin-3 RVKRFWPLVPVAINTVAAGINLYK 1899 (chCATH-3, bird AIRRK cathelicidin, chicken cathelicidin) AP01007 2JMY, CM15 KWKLFKKIGAVLKVL 1900 (Synthetic) AP00728 2jni, Arenicin-2 RWCVYAYVRIRGVLVRYRRCW 1901 (marine polychaeta, BBBm) AP00473 2jos, Piscidin 1 FFHHIFRGIVHVGKTIHRLVTG 1902 (fish) AP01151 2JPJ, Lactococcin GTWDDIGQGIGRVAYWVGKALGN 1903 G-a (chain a, class  LSDVNQASRINRKKKH IIb bacteriocin, bacteria. For chain b, see info) AP00757 2jpy, Phylloseptin- FLSLIPHAINAVSTLVHHF 1904 H2 (PLS-H2, Phylloseptin-2, PS- 2)(XXA, frog) AP00546 2jq0, Phylloseptin- FLSLIPHAINAVSAIAKHN 1905 1 (Phylloseptin-H1, PLS-H1, PS-1, XXA, frog) AP00758 2jq1, Phylloseptin- FLSLIPHAINAVSALANHG 1906 3 (Phylloseptin-H3, PLS-H3, PS-3) (XXA, frog) AP00727 2jsb, Arenicin-1 RWCVYAYVRVRGVLVRYRRCW 1907 (marine polychaeta, BBBm) AP00592 2k10, Ranatuerin- GILSSFKGVAKGVAKDLAGKLLET 1908 2CSa (frog) LKCKITGC AP00485 2K38, Cupiennin GFGALFKFLAKKVAKTVAKQAAK 1909 1a (spider) QGAKYVVNKQME AP00310 2K6O, Human LL- LLGDFFRKSKEKIGKEFKRIVQRIK 1910 37 (LL37, human DFLRNLVPRTES cathelicidin; released by proteinase 3 from its precursor in neutrophils; FALL- 39; BBB, BBM, BBP, BBW, BBD, BBL, ZZHh) AP00199 2LEU, Leucocin_A KYYGNGVHCTKSGCSVNWGEAFS 1911 (LeuA, class IIa AGVHRLANGGNGFW bacteriocin, bacteria) AP00144 2MAG, Magainin 2 GIGKFLHSAKKFGKAFVGEIMNS 1912 (frog) AP00146 2MLT, Melittin GIGAVLKVLTTGLPALISWIKRKRQ 1913 (insect, ZZHa) Q AP01010 2PCO, Latarcin 1 SMWSGMWRRKLKKLRNALKKKL 1914 (Ltc1, BBM, KGEK spider) AP00176 2PM1, human ACYCRIPACIAGERRYGTCIYQGRL 1915 alpha Defensin WAFCC HNP-1 (human neutrophil peptide- 1, HNP1, human defensin, ZZHh) AP01158 2RLG, RP-1 ALYKKFKKKLLKSLKRL 1916 (synthetic) AP00102 8TFV, Thanatin GSKKPVPIIYCNRRTGKCQRM 1917 (insect) AP00995 A58718, Carnocin GSEIQPR 1918 UI49 (bacteria) AP01002 AAC18827, KSWSLCTPGCARTGSFNSYCC 1919 Mutacin III (mutacin 1140, bacteria) AP00987 ABI74601, Arasin SRWPSPGRPRPFPGRPKPIFRPRPCN 1920 1 (Crustacea) CYAPPCPCDRW AP01000 CAA63706, GSGVIPTISHECHMNSFQFVFTCCS 1921 variacin (lantibiotic, class I bacteriocin, bacteria) AP00361 O15946, Lebocin 4 DLRFWNPREKLPLPTLPPFNPKPIYI 1922 (insect, silk moth) DMGNRY AP00343 O16825, Andropin VFIDILDKMENAIHKAAQAGIGIAK 1923 (insect, fruit fly) PIEKMILPK AP00417 O17513, SIGTAVKKAVPIAKKVGKVAIPIAK 1924 Ceratotoxin D AVLSVVGQLVG (insect, fly) AP00435 O18494, Styelin C GWFGKAFRSVSNFYKKHKTYIHA 1925 (sea squirt, GLSAATLL tunicate, XXA) AP00330 O18495, Styelin D GWLRKAAKSVGKFYYKHKYYIKA 1926 (Sea squirt, AWQIGKHAL tunicate, XXA) AP00331 O18495, Styelin E GWLRKAAKSVGKFYYKHKYYIKA 1927 (Sea squirt, AWKIGRHAL tunicate, XXA) AP01001 O54329, Mutacin II NRWWQGVVPTVSYECRMNSWQH 1928 (lantibiotic, VFTCC mutacin H-29B, J- T8, class I bacteriocin, bacteria) AP00342 O81338, AKCIKNGKGCREDQGPPFCCSGFC 1929 Antimicrobial YRQVGWARGYCKNR peptide 1 (plant) AP00373 O96059, Moricin 2 AKIPIKAIKTVGKAVGKGLRAINIA 1930 (insect) STANDVFNFLKPKKRKH AP00449 P01190, SYSMEHFRWGKPV 1931 Melanotropin alpha (Alpha-MSH) AP00187 P01376, VVCACRRALCLPRERRAGFCRIRG 1932 CORTICOSTATIN RIHPLCCRR III (MCP-1, rabbit neutrophil peptide 1, NP-1)(animal defensin, alpha- defensin, rabbit) AP00188 P01377, VVCACRRALCLPLERRAGFCRIRG 1933 CORTICOSTATIN RIHPLCCRR IV (MCP-2, rabbit neutrophil defensin 2, NP-2, animal defensin, rabbit) AP00049 P01505, Bombinin GIGALSAKGALKGLAKGLAEHFAN 1934 (toad) AP00139 P01507, Cecropin KWKLFKKIEKVGQNIRDGIIKAGP 1935 A (insect, ZZHa) AVAVVGQATQIAK AP00128 P01509, Cecropin KWKIFKKIEKVGRNIRNGIIKAGPA 1936 B (insect, silk VAVLGEAKAL moth) AP00131 P01511, Cecropin WNPFKELERAGQRVRDAIISAGPA 1937 D (insect, moth) VATVAQATALAK AP00136 P01518, Crabro lin  FLPLILRKIVTAL 1938 (insect, XXA) AP00183 P04142, Cecropin RWKIFKKIEKMGRNIRDGIVKAGP 1939 B (insect) AIEVLGSAKAI AP00448 P04205, INLKAIAALAKKLL 1940 Mastoparan M (MP-M, insect, XXA) AP00234 P06833, SDEKASPDKHHRFSLSRYAKLANR 1941 Seminalplasmin LANPKLLETFLSKWIGDRGNRSV (SPLN, calcium transporter inhibitor, caltrin, cow) AP00314 P07466, Rabbit VFCTCRGFLCGSGERASGSCTINGV 1942 neutrophil peptide RHTLCCRR 5 (NP-5, animal defensin, alpha- defensin) AP00189 P07467, Rabbit VSCTCRRFSCGFGERASGSCTVNG 1943 neutrophil peptide VRHTLCCRR 4 (NP-4) AP00186 P07468, GRCVCRKQLLCSYRERRIGDCKIR 1944 CORTICOSTATIN GVRFPFCCPR II (Rabbit neutrophil peptide 3b (NP-3b, rabbit) AP00185 P07469, ICACRRRFCPNSERFSGYCRVNGA 1945 CORTICOSTATIN RYVRCCSRR I (rabbit) AP00217 P07469, Rabbit GICACRRRFCPNSERFSGYCRVNG 1946 neutrophil defensin ARYVRCCSRR 3a (NP-3a, animal defensin, alpha- defensin) AP00067 P07493, SKITDILAKLGKVLAHV 1947 Bombolitin II (insect, bee) AP00068 P07494, IKIMDILAKLGKVLAHV 1948 Bombolitin III (insect, bee) AP00069 P07495, INIKDILAKLVKVLGHV 1949 Bombolitin IV (insect, bee) AP00070 P07496, INVLGILGLLGKALSHL 1950 Bombolitin V (insect, bee) AP00236 P07504, Pyrularia KSCCRNTWARNCYNVCRLPGTISR 1951 thionin (Pp-TH, EICAKKCDCKIISGTTCPSDYPK plant) AP00230 P08375, Sarcotoxin GWLKKIGKKIERVGQHTRDATIQG 1952 IA (insect, flesh LGIAQQAANVAATAR AP00231 P08376, Sarcotoxin GWLKKIGKKIERVGQHTRDATIQV 1953 IB (insect, flesh IGVAQQAANVAATAR AP00232 P08377, Sarcotoxin GWLRKIGKKIERVGQHTRDATIQV 1954 IC (insect, flesh LGIAQQAANVAATAR AP00066 P10521, IKITTMLAKLGKVLAHV 1955 Bombolitin I (insect, bee) AP00206 P10946, Lantibiotic WKSESLCTPGCVTGALQTCFLQTL 1956 subtilin (class I TCNCKISK bacteriocin, bacteria) AP00312 P11477, Cryptdin-2 LRDLVCYCRARGCKGRERMNGTC 1957 (Crp2, animal RKGHLLYMLCCR defensin, alpha, mouse) AP00205 P13068, Nisin A ITSISLCTPGCKTGALMGCNMKTA 1958 (lantibiotic, class I  TCHCSIHVSK bacteriocin, bacteria) AP00215 P14214, RWCFRVCYRGICYRKCR 1959 Tachyplesin II (crabs, Crustacea) AP00212 P14216, RRWCFRVCYKGFCYRKCR 1960 Polyphemusin II (crabs, Crustacea, XXA, ZZHa. Derivatives: T22) AP00134 P14661, Cecropin SWLSKTAKKLENSAKKRISEGIAIA 1961 P1 (pig) IQGGPR AP00011 P14662, WNPFKELERAGQRVRDAVISAAPA 1962 Bactericidin B2 VATVGQAAAIARG (insect) AP00032 P14663, WNPFKELERAGQRVRDAIISAGPA 1963 Bactericidin B-3 VATVGQAAAIARG (insect) AP00033 P14664, WNPFKELERAGQRVRDAIISAAPA 1964 Bactericidin B-4 VATVGQAAAIARG (insect) AP00034 P14665, WNPFKELERAGQRVRDAVISAAA 1965 Bactericidin B-5P VATVGQAAAIARG (insect) AP00125 P14666, Cecropin RWKIFKKIEKVGQNIRDGIVKAGP 1966 (insect, silk moth) AVAVVGQAATI AP00002 P15450, YVPLPNVPQPGRRPFPTFPGQGPFN 1967 ABAECIN (insect, PKIKWPQGY honeybee) AP00505 P15516, human DSHAKRHHGYKRKFHEKHHSHRG 1968 Histatin 5 (ZZHs; Y derivatives Dh-5) AP00520 P15516, human DSHAKRHHGYKRKFHEKHHSHRG 1969 Histatin 3 YRSNYLYDN AP00523 P15516, human KFHEKHHSHRGY 1970 Histatin 8 AP00226 P17722, Royalisin VTCDLLSFKGQVNDSACAANCLSL 1971 (insect, honeybee) GKAGGHCEKVGCICRKTSFKDLW DKRF AP00213 P18252, KWCFRVCYRGICYRKCR 1972 Tachyplesin III (horseshoe crabs, Crustacea) AP00233 P18312, Sarcotoxin GWIRDFGKRIERVGQHTRDATIQTI 1973 ID (insect, flesh AVAQQAANVAATLKG AP00207 P19578, Lantibiotic TAGPAIRASVKQCQKTLKATRLFT 1974 PEPS (class I VSCKGKNGCK bacteriocin, bacteria) AP00009 P19660, RFRPPIRRPPIRPPFYPPFRPPIRPPIF 1975 BACTENECIN 5 PPIRPPFRPPLGPFP (bac5, cow cathelicidin) AP00010 P19661, RRIRPRPPRLPRPRPRPLPFPRPGPR 1976 BACTENECIN 7 PIPRPLPFPRPGPRPIPRPLPFPRPGP (bac7, cow RPIPRPL cathelicidin) AP00200 P21564, LKLKSIVSWAKKVL 1977 Mastoparan B (MP-B, insect, XXA) AP00005 P21663, Andropin VFIDILDKVENAIHNAAQVGIGFAK 1978 (insect, fly) PFEKLINPK AP00008 P22226, Cyclic RLCRIVVIRVCR 1979 dodecapeptide (cow cathelicidin) AP01205 P23826, Lactocin S STPVLASVAVSMELLPTASVLYSD 1980 (XXD3, bacteria) VAGCFKYSAKHHC AP00239 P24335, XPF (the GWASKIGQTLGKIAKVGLKELIQP 1981 xenopsin precursor K fragment, African clawed frog) AP00235 P25068, Bovine NPVSCVRNKGICVPIRCPGSMKQIG 1982 tracheal TCVGRAVKCCRKK antimicrobial peptide (TAP, cow) AP00418 P25230, CAP18 GLRKRLRKFRNKIKEKLKKIGQKIQ 1983 (rabbit cathelicidin,  GFVPKLAPRTDY BBL) AP00203 P25403, Mj-AMP1 QCIGNGGRCNENVGPPYCCSGFCL 1984 (MjAMP1, plant RQPGQGYGYCKNR defensin) AP00202 P25404, Mj-AMP2 CIGNGGRCNENVGPPYCCSGFCLR 1985 (MjAMP2, plant QPNQGYGVCRNR defensin) AP00138 P28310, Cryptdin-3 LRDLVCYCRKRGCKRRERMNGTC 1986 (Crp3, animal RKGHLMYTLCCR defensin, alpha, mouse) AP00184 P28794, MBP-1 RSGRGECRRQCLRRHEGQPWETQ 1987 (plant) ECMRRCRRRG AP00050 P29002, Bombinin- GIGASILSAGKSALKGLAKGLAEHF 1988 like peptide 1 AN (BLP-1, toad) AP00051 P29003, Bombinin- GIGSAILSAGKSALKGLAKGLAEHF 1989 like peptide 2 AN (BLP-2, toad) AP00052 P29004, Bombinin- GIGAAILSAGKSALKGLAKGLAEH 1990 like peptide 3 F (BLP-3, XXA, toad) AP00053 P29005, Bombinin- GIGAAILSAGKSIIKGLANGLAEHF 1991 like peptide 4 (BLP-4, toad) AP00634 P29430, Pediocin KYYGNGVTCGKHSCSVDWGKATT 1992 PA-1/ AcH CIINNGAMAWATGGHQGNHKC (PedPA1, class IIA bacteriocin, bacteria) AP00204 P29559, Nisin Z ITSISLCTPGCKTGALMGCNMKTA 1993 (lantibiotic, class I TCNCSIHVSK bacteriocin, bacteria) AP00130 P29561, Cecropin GWLKKLGKRIERIGQHTRDATIQG 1994 C (insect, fly) LGIAQQAANVAATAR AP00001 P31107, GLWSKIKEVGKEAAKAAAKAAGK 1995 ADENOREGULIN AALGAVSEAV (Dermaseptin B2, Dermaseptin-B2, DRS-B2, DRS B2, frog) AP00228 P31529, Sapecin_B LTCEIDRSLCLLHCRLKGYLRAYCS 1996 (insect, flesh fly) QQKVCRCVQ AP00229 P31530, Sapecin C ATCDLLSGIGVQHSACALHCVFRG 1997 (insect, flesh fly) NRGGYCTGKGICVCRN AP00218 P32195, Protegrin RGGRLCYCRRRFCICV 1998 2 (PG-2, pig cathelicidin) AP00219 P32196, Protegrin RGGGLCYCRRRFCVCVGR 1999 3 (PG-3, pig cathelicidin) AP00073 P32412, Brevinin- FLPLLAGLAANFLPKIFCKITRKC 2000 1E (frog) AP00080 P32414, GIFSKLGRKKIKNLLISGLKNVGKE 2001 Esculentin-1 (frog) VGMDVVRTGIDIAGCKIKGEC AP00074 P32423, Brevinin-1 FLPVLAGIAAKVVPALFCKITKKC 2002 (frog) AP00075 P32424, Brevinin-2 GLLDSLKGFAATAGKGVLQSLLST 2003 (frog) ASCKLAKTC AP00175 P34084, Macaque DSHEERHHGRHGHHKYGRKFHEK 2004 histatin (M-Histatin HHSHRGYRSNYLYDN 1, primate, monkey) AP00006 P35581, Apidaecin GNNRPVYIPQPRPPHPRI 2005 IA (insect, honeybee) AP00007 P35581, Apidaecin GNNRPVYIPQPRPPHPRL 2006 IB (insect, honeybee) AP00414 P36190, SIGSALKKALPVAKKIGKIALPIAK 2007 Ceratotoxin A AALP (insect, fly) AP00415 P36191, SIGSAFKKALPVAKKIGKAALPIAK 2008 Ceratotoxin B AALP (insect, fly) AP00172 P36193, Drosocin GKPRPYSPRPTSHPRPIRV 2009 (insect) AP00170 P37362, VDKGSYLPRPTPPRPIYNRN 2010 Pyrrhocoricin (insect) AP00635 P38577, KYYGNGVHCTKSGCSVNWGEAAS 2011 Mesentericin Y105 AGIHRLANGGNGFW (MesY105, class IIA bacteriocin, bacteria) AP00636 P38579, AISYGNGVYCNKEKCWVNKAENK 2012 Camobacteriocin QAITGIVIGGWASSLAGMGH BM1 (CnbBM1, PiscV1b, class IIA bacteriocin, bacteria) AP00209 P39080, Peptide GVLSNVIGYLKKLGTGALNAVLK 2013 PGQ (frog) Q AP00513 P39084, Ranalexin FLGGLIKIVPAMICAVTKKC 2014 (frog) AP00071 P40835, Brevinin- FLPAIFRMAAKVVPTIICSITKKC 2015 1EA (frog) AP00072 P40836, Brevinin- VIPFVASVAAEMQHVYCAASRKC 2016 1EB (frog) AP00076 P40837, Brevinin- GILDTLKNLAISAAKGAAQGLVNK 2017 2EA (frog) ASCKLSGQC AP00077 P40838, Brevinin- GILDTLKNLAKTAGKGALQGLVK 2018 2EB (frog) MASCKLSGQC AP00078 P40839, Brevinin- GILLDKLKNFAKTAGKGVLQSLLN 2019 2EC (frog) TASCKLSGQC AP00079 P40840, Brevinin- GILDSLKNLAKNAGQILLNKASCK 2020 2ED (frog) LSGQC AP00081 P40843, GIFSKLAGKKIKNLLISGLKNVGKE 2021 Esculentin-1A VGMDVVRTGIDIAGCKIKGEC (frog) AP00082 P40844, GIFSKLAGKKLKNLLISGLKNVGK 2022 Esculentin-1B EVGMDVVRTGIDIAGCKIKGEC (frog) AP00083 P40845, GIL SLVKGVAKLAGKGLAKE GGKF 2023 Esculentin-2A GLELIACKIAKQC (frog) AP00084 P40846, GIFSLVKGAAKLAGKGLAKEGGKF 2024 Esculentin-2B GLELIACKIAKQC (ES2B_RANES, frog) AP00299 P46156, Chicken GRKSDCFRKSGFCAFLKCPSLTLIS 2025 gallinacin 1 (Gal 1,  GKCSRFYLCCKRIW avian beta- defensin, bird) AP00300 P46157, Gallinacin GRKSDCFRKNGFCAFLKCPYLTLIS 2026 1 alpha (avian beta-  GKCSRFHLCCKRIW defensin, Bird), AP00298 P46158, Chicken LFCKGGSCHFGGCPSHLIKVGSCFG 2027 gallinacin 2 (Gal 2,  FRSCCKWPWNA avian beta- defensin, bird) AP00037 P46160, Beta- VRNHVTCRINRGFCVPIRCPGRTRQ 2028 defensin 2 (cow) IGTCFGPRIKCCRSW AP00038 P46161, Beta- QGVRNHVTCRINRGFCVPIRCPGR 2029 defensin 3 (cow) TRQIGTCFGPRIKCCRSW AP00039 P46162, Beta- QRVRNPQSCRWNMGVCIPFLCRV 2030 defensin 4 (cow) GMRQIGTCFGPRVPCCRR AP00040 P46163, Beta- QVVRNPQSCRWNMGVCIPISCPGN 2031 defensin 5 (cow) MRQIGTCFGPRVPCCRRW AP00041 P46164, Beta- QGVRNHVTCRIYGGFCVPIRCPGR 2032 defensin 6 (cow) TRQIGTCFGRPVKCCRRW AP00042 P46165, Beta- QGVRNFVTCRINRGFCVPIRCPGHR 2033 defensin 7 (cow) RQIGTCLGPRIKCCR AP00043 P46166, Beta- VRNFVTCRINRGFCVPIRCPGHRRQ 2034 defensin 8 (cow) IGTCLGPQIKCCR AP00044 P46167, Beta- QGVRNFVTCRINRGFCVPIRCPGHR 2035 defensin 9 (cow) RQIGTCLAPQIKCCR AP00045 P46168, Beta- QGVRSYLSCWGNRGICLLNRCPGR 2036 defensin 10 (cow)  MRQIGTCLAPRVKCCR AP00046 P46169, Beta- GPLSCRRNGGVCIPIRCPGPMRQIG 2037 defensin 11 (cow)  TCFGRPVKCCRSW AP00048 P46171, Bovine SGISGPLSCGRNGGVCIPIRCPVPM 2038 beta-defensin 13 RQIGTCFGRPVKCCRSW (cow) AP 00350 P48821, Enbocin PWNIFKEIERAVARTRDAVISAGPA 2039 (insect, moth) VRTVAAATSVAS AP00173 P49112, GNCP-2 RCICTTRTCRFPYRRLGTCLFQNRV 2040 (Guinea pig YTFCC neutrophil cationic peptide 2) AP00369 P49930, PMAP-23 RIIDLLWRVRRPQKPKFVTVWVR 2041 (PMAP23, pig cathelicidin) AP00370 P49931, PMAP-36 VGRFRRLRKKTRKRLKKIGKVLK 2042 (PMAP36, pig WIPPIVGSIPLGCG cathelicidin) AP00371 P49932, PMAP-37 GLLSRLRDFLSDRGRRLGEKIERIG 2043 (PMAP37, pig QKIKDLSEFFQS cathelicidin) AP00220 P49933, Protegrin RGGRLCYCRGWICFCVGR 2044 4 (PG-4, pig cathelicidin) AP00221 P49934, Protegrin RGGRLCYCRPRFCVCVGR 2045 5 (PG-5, pig cathelicidin) AP00346 P50720, Hyphancin RWKIFKKIERVGQNVRDGIIKAGP 2046 IIID (Fall AIQVLGTAKAL webworm, insect) AP00347 P50721, Hyphancin RWKFFKKIERVGQNVRDGLIKAGP 2047 IIIE (Fall AIQVLGAAKAL webworm, insect) AP00348 P50722, Hyphancin RWKVFKKIEKVGRNIRDGVIKAGP 2048 IIIF (Fall AIAVVGQAKAL webworm, insect) AP00349 P50723, Hyphancin RWKVFKKIEKVGRHIRDGVIKAGP 2049 IIIG (Fall AITVVGQATAL webworm, insect) AP00281 P51473, mCRAMP GLLRKGGEKIGEKLKKIGQKIKNFF 2050 (mouse QKLVPQPEQ cathelicidin; derivatives: CRAMP 18) AP00366 P54228, BMAP-27 GRFKRFRKKFKKLFKKLSPVIPLLH 2051 (BMAP27, cow LG cathelicidin, ZZHs, derivatives BMAP- 18 and BMAP-15) AP00367 P54229, BMAP-28 GGLRSLGRKILRAWKKYGPIIVPIIR 2052 (BMAP28, cow IG cathelicidin) AP00450 P54230, Cyclic RICRIIFLRVCR 2053 dodecapeptide (sheep cathelicidin) AP00359 P54684, Lebocin DLRFLYPRGKLPVPTPPPFNPKPIYI 2054 1/2 (insect, silk DMGNRY moth) AP00360 P55796, Lebocin 3 DLRFLYPRGKLPVPTLPPFNPKPIYI 2055 (insect, silk moth) DMGNRY AP00307 P55897, Buforin I AGRGKQGGKVRAKAKTRSSRAGL 2056 (toad) QFPVGRVHRLLRKGNY AP00308 P55897, Buforin II TRSSRAGLQFPVGRVHRLLRK 2057 (toad) AP00240 P56226, Caerin 1.1 GLLSVLGSVAKHVLPHVVPVIAEH 2058 (frog, ZZHa) L AP00241 P56227, Caerin 1.2 GLLGVLGSVAKHVLPHVVPVIAEH 2059 (frog) L AP00242 P56228, Caerin 1.3 GLLSVLGSVAQHVLPHVVPVIAEH 2060 (frog) L AP00243 P56229, Caerin 1.4 GLLSSLSSVAKHVLPHVVPVIAEHL 2061 (frog) AP00244 P56230, Caerin 1.5 GLLSVLGSVVKHVIPHVVPVIAEHL 2062 (frog) AP00245 P56231, Caerin 1.6 GLFSVLGAVAKHVLPHVVPVIAEK 2063 (frog) AP00246 P56232, Caerin 1.7 GLFKVLGSVAKHLLPHVAPVIAEK 2064 (frog) AP00249 P56233, Caerin 2.1 GLVSSIGRALGGLLADVVKSKGQP 2065 (frog) A AP00250 P56234, Caerin 2.2 GLVSSIGRALGGLLADVVKSKEQP 2066 (frog) A AP00251 P56236, Caerin 2.4 GLVSSIGKALGGLLADVVKTKEQP 2067 (frog) A AP00252 P56236, Caerin 2.5 GLVSSIGRALGGLLADVVKSKEQP 2068 (frog) A AP00253 P56238, Caerin 3.1 GLWQKIKDKASELVSGIVEGVK 2069 (frog) AP00254 P56238, Caerin 3.2 GLWEKIKEKASELVSGIVEGVK 2070 (frog) AP00255 P56240, Caerin 3.3 GLWEKIKEKANELVSGIVEGVK 2071 (frog) AP00256 P56241, Caerin 3.4 GLWEKIREKANELVSGIVEGVK 2072 (frog) AP00257 P56242, Caerin 4.1 GLWQKIKSAAGDLASGIVEGIKS 2073 (frog) AP00258 P56243, Caerin 4.2 GLWQKIKSAAGDLASGIVEAIKS 2074 (frog) AP00259 P56244, Caerin 4.3 GLWQKIKNAAGDLASGIVEGIKS 2075 (frog) AP00434 P56249, Frenatin 3 GLMSVLGHAVGNVLGGLFKS 2076 (frog) AP00272 P56386, Murine DQYKCLQHGGFCLRSSCPSNTKLQ 2077 beta-defensin 1 GTCKPDKPNCCKS (mBD-1, mouse) AP00368 P56425, BMAP-34 GLFRRLRDSIRRGQQKILEKARRIG 2078 (BMAP34, cow ERIKDIFRG cathelicidin) AP00273 P56685, Buthinin SIVPIRCRSNRDCRRFCGFRGGRCT 2079 (Sahara scorpion) YARQCLCGY AP00282 P56872, SIPCGESCVFIPCTVTALLGCSCKSK 2080 Cyclopsychotride VCYKN A (CPT, plant cyclotides, XXC) AP00094 P56917, Temporin FLPLIGRVLSGIL 2081 A (XXA, frog) AP00096 P56918, Temporin LLPILGNLLNGLL 2082 C (XXA, frog) AP00097 P56920, Temporin VLPIIGNLLNSLL 2083 E (XXA,frog) AP00098 P56921, Temporin FLPLIGKVLSGIL 2084 F (XXA,frog) AP00100 P56923, Temporin LLPNLLKSLL 2085 K (XXA,frog) AP00295 P56928, eNAP-2 EVERKHPLGGSRPGRCPTVPPGTF 2086 (horse) GHCACLCTGDASEPKGQKCCSN AP00101 P57104, Temporin FVQWFSKFLGRIL 2087 L (XXA,frog) AP00095 P79874, Temporin LLPIVGNLLKSLL 2088 B (XXA, frog) AP00099 P79875, Temporin  FFPVIGRILNGIL 2089 G (XXA,frog) AP00413 P80032, SLQGGAPNFPQPSQQNGGWQVSP 2090 Coleoptericin DLGRDDKGNTRGQIEIQNKGKDH (insect) DFNAGWGKVIRGPNKAKPTWHVG GTYRR AP00396 P80054, PR-39 RRRPRPPYLPRPRPPPFFPPRLPPRIP 2091 (PR39, pig PGFPPRFPPRFP cathelicidin) AP00182 P80154, Insect GFGCPLDQMQCHRHCQTITGRSGG 2092 defensin YCSGPLKLTCTCYR AP00444 P80223, GICACRRRFCLNFEQFSGYCRVNG 2093 Corticostatin VI  ARYVRCCSRR (CS-VI) (animal defensin, rabbit) AP00208 P80230, Peptide RADTQTYQPYNKDWIKEKIYVLLR 2094 3910 (pig) RQAQQAGK AP00157 P80277, ALWKTMLKKLGTMALHAGKAAL 2095 Dermaseptin-S1 GAAADTISQGTQ (Dermaseptin S1, DRS S1, DRS-S1, frog) AP00158 P80278, ALWFTMLKKLGTMALHAGKAAL 2096 Dermaseptin-S2 GAAANTISQGTQ (Dermaseptin S2, DRS S2, DRS-S2, frog) AP00159 P80279, ALWKNMLKGIGKLAGKAALGAV 2097 Dermaseptin-S3 KKLVGAES (Dermaseptin S3, DRS S3, DRS-S3, frog) AP00160 P80280, ALWMTLLKKVLKAAAKALNAVL 2098 Dermaseptin-S4 VGANA (Dermaseptin S4, DRS S4, DRS-S4, frog) AP00161 P80281, GLWSKIKTAGKSVAKAAAKAAVK 2099 Dermaseptin-S5 AVTNAV (Dermaseptin S5, DRS S5, DRS-S5, frog) AP00293 P80282, AMWKDVLKKIGTVALHAGKAAL 2100 Dermaseptin-B1 GAVADTISQ (DRS-B1, DRS B1, frog) AP00264 P80389, Chicken GRKSDCFRKSGFCAFLKCPSLTLIS 2101 Heterophil Peptide GKCSRFYLCCKRIR 1 (CHP1, bird, animal) AP00265 P80390, Chicken GRKSDCFRKNGFCAFLKCPYLTLIS 2102 Heterophil Peptide GLCSFHLC 2 (CHP2, bird, animal) AP00266 P80391, Turkey GKREKCLRRNGFCAFLKCPTLSVIS 2103 Heterophil Peptide GTCSRFQVCC 1 (THP1, turkey) AP00267 P80392, Turkey LFCKRGTCHFGRCPSHLIKVGSCFG 2104 Heterophil Peptide FRSCCKWPWDA 2 (THP2, bird, anaimal) AP00269 P80393, Turkey LSCKRGTCHFGRCPSHLIKGSCSGG 2105 Heterophil Peptide 3 (THP3, bird, animal) AP00085 P80395, Gaegurin- SLFSLIKAGAKFLGKNLLKQGACY 2106 1 (Gaegurin 1, AACKASKQC frog) AP00086 P80396, Gaegurin- GIMSIVKDVAKNAAKEAAKGALST 2107 2 (Gaegurin 2, LSCKLAKTC frog) AP00087 P80397, Gaegurin- GIMSIVKDVAKTAAKEAAKGALST 2108 3 (Gaegurin 3, LSCKLAKTC frog) AP00089 P80399, Gaegurin- FLGALFKVASKVLPSVFCAITKKC 2109 5 (Gaegurin 5, frog) AP00090 P80400, Gaegurin- FLPLLAGLAANFLPTIICKISYKC 2110 6 (Gaegurin 6, frog) AP00362 P80408, VDKPDYRPRPRPPNM 2111 Metalnikowin I (insect) AP00363 P80409, VDKPDYRPRPWPRPN 2112 Metalnikowin IIA (insect) AP00364 P80410, VDKPDYRPRPWPRNMI 2113 Metalnikowin IIB (insect) AP00365 P80411, VDKPDYRPRPWPRPNM 2114 Metalnikowin III (insect) AP00632 P80569, Piscicolin KYYGNGVSCNKNGCTVDWSKAIG 2115 126 / Piscicocin IIGNNAAANLTTGGAAGWNKG Via (PiscV1a, Pisc126, class IIA bacteriocin, bacteria) AP01003 P80666, Mutacin FKSWSFCTPGCAKTGSFNSYCC 2116 B-Ny266 (bacteria) AP00276 P80710, Clavanin VFQFLGKIIHHVGNFVHGFSHVF 2117 A (urochordates, sea squirts, and sea pork, tunicate) AP00277 P80711, Clavanin VFQFLGRIIHHVGNFVHGFSHVF 2118 B (Sea squirt, tunicate) AP00278 P80712, Clavanin VFHLLGKIIHHVGNFVYGFSHVF 2119 C (Sea squirt, tunicate) AP00279 P80713, Clavanin AFKLLGRIIHHVGNFVYGFSHVF 2120 D (Sea squirt, tunicate) AP00280 P80713, Clavanin LFKLLGKIIHHVGNFVHGFSHVF 2121 D (Sea squirt, tunicate) AP00294 P80930, eNAP-1 DVQCGEGHFCHDQTCCRASQGGA 2122 (horse) CCPYSQGVCCADQRHCCPVGF AP00400 P80952, Skin YPPKPESPGEDASPEEMNKYLTAL 2123 peptide tyrosine- RHYINLVTRQRY tyrosine (skin- PYY, SPYY, frog) AP00091 P80954, Rugosin A GLLNTFKDWAISIAKGAGKGVLTT 2124 (frog) LSCKLDKSC AP00092 P80955, Rugosin B SLFSLIKAGAKFLGKNLLKQGAQY 2125 (frog) AACKVSKEC AP00093 P80956, Rugosin C GILDSFKQFAKGVGKDLIKGAAQG 2126 (frog) VLSTMSCKLAKTC AP00392 P81056, Penaeidin- YRGGYTGPIPRPPPIGRPPLRLVVC 2127 1 (shrimp, ACYRLSVSDARNCCIKFGSCCHLV Crustacea) K AP00393 P81057, Penaeidin- YRGGYTGPIPRPPPIGRPPFRPVCN 2128 2a (shrimp, ACYRLSVSDARNCCIKFGSCCHLV Crustacea) K AP00394 P81058, Penaeidin- QVYKGGYTRPIPRPPPFVRPLPGGP 2129 3a (shrimp, IGPYNGCPVSCRGISFSQARSCCSR Crustacea) LGRCCHVGKGYS AP00247 P81251, Caerin 1.8 GLFKVLGSVAKHLLPHVVPVIAEK 2130 (frog) AP00248 P81252, Caerin 1.9 GLFGVLGSIAKHVLPHVVPVIAEK 2131 (frog, ZZHa) AP00126 P81417, Cecropin GGLKKLGKKLEGVGKRVFKASEK 2132 A (insect, ALPVAVGIKALG mosquito) AP00169 P81437, Formaecin GRPNPVNTKPTPYPRL 2133 2 (insect, ants) AP00168 P81438, Formaecin GRPNPVNNKPTPHPRL 2134 1 (insect, ants) AP00296 P81456, Fabatin-1 LLGRCKVKSNRFHGPCLTDTHCST 2135 (plant defensin) VCRGEGYKGGDCHGLRRRCMCLC AP00297 P81457, Fabatin-2 LLGRCKVKSNRFNGPCLTDTHCST 2136 (plant defensin) VCRGEGYKGGDCHGLRRRCMCLC AP01215 P81463, European FVPYNPPRPYQSKPFPSFPGHGPFN 2137 bumblebee abaecin PKIQWPYPLPNPGH (insect) AP01214 P81464, Apidaecin GNRPVYIPPPRPPHPRL 2138 (insect) AP00440 P81465, defensin VTCFCRRRGCASRERHIGYCRFGN 2139 HANP-1 (hamster) TIYRLCCRR AP00441 P81466, defensin CFCKRPVCDSGETQIGYCRLGNTF 2140 HANP-2 (hamster) YRLCCRQ AP00442 P81467, defensin VTCFCRRRGCASRERLIGYCRFGN 2141 HANP-3 (hamster) TIYGLCCRR AP00439 P81468, defensin VTCFCKRPVCDSGETQIGYCRLGN 2142 HANP-4 (hamster) TFYRLCCRQ AP00328 P81469, Styelin A GFGKAFHSVSNFAKKHKTA 2143 (Sea squirt, tunicate, XXA) AP00329 P81470, Styelin B GFGPAFHSVSNFAKKHKTA 2144 (Sea squirt, tunicate, XXA) AP00492 P81474, Misgurin RQRVEELSKFSKKGAAARRRK 2145 (fish) AP00165 P81485, ALWKNMLKGIGKLAGQAALGAV 2146 Dermaseptin-B3 KTLVGAE (Dermaseptin B3, DRS-B3, DRS B3, frog) AP00163 P81486, ALWKDILKNVGKAAGKAVLNTVT 2147 Dermaseptin-B4 DMVNQ (Dermaseptin B4, DRS-B4, DRS B4, DRS-TR1, IRP, frog) AP00162 P81487, GLWNKIKEAASKAAGKAALGFVN 2148 Dermaseptin-B5 EMV (Dermaseptin B5, DRS-B5, DRS B5, frog) AP00164 P81488, ALWKTIIKGAGKMIGSLAKNLLGS 2149 Dermaseptin-B9 QAQPES (Dermaseptin B9, DRS-B9, DRS DRG3, frog) AP00167 P81565, Phylloxin GWMSKIASGIGTFLSGMQQ 2150 (phylloxin-B1, PLX-B1, XXA, frog) AP00291 P81568, Defensin MFFSSKKCKTVSKTFRGPCVRNAN 2151 D5 (So-D5) (plant defensin) AP00290 P81569, Defensin MFFSSKKCKTVSKTFRGPCVRNA 2152 D4 (So-D4) (plant defensin) AP00289 P81570, Defensin GIFSSRKCKTVSKTFRGICTRNANC 2153 D3 (So-D3) (plant defensin) AP00288 P81572, Defensin TCESPSHKFKGPCATNRNCES 2154 Dl (So-D1) (plant defensin) AP00292 P81573, Defensin GIFSSRKCKTPSKTFKGYCTRDSNC 2155 D7 (So-D7) (plant  DTSCRYEGYPAGD defensin) AP00270 P81591, Pn-AMP QQCGRQASGRLCGNRLCCSQWGY 2156 (PnAMP, plant CGSTASYCGAGCQSQCRS defensin) AP00412 P81592, SLQPGAPNVNNKDQPWQVSPHISR 2157 Acaloleptin A1 DDSGNTRTDINVQRHGENNDFEAG (insect) WSKVVRGPNKAKPTWHIGGTHRW AP00433 P81605, human SSLLEKGLDGAKKAVGGLGKLGK 2158 Dermcidin (DCD- DAVEDLESVGKGAVHDVKDVLDS 1) V AP00332 P81612, Mytilin A GCASRCKAKCAGRRCKGWASASF 2159 (Blue mussel) RGRCYCKCFRC AP00333 P81613, Mytilin B SCASRCKGHCRARRCGYYVSVLY 2160 (Blue mussel) RGRCYCKCLRC AP00334 P81613, FFHHIFRGIVHVGKTIHKLVTG 2161 Moronecidin (fish) AP00351 P81835, Citropin GLFDVIKKVASVIGGL 2162 1.1 (amphibian, frog) AP00352 P81840, Citropin GLFDIIKKVASVVGGL 2163 1.2 (amphibian, frog) AP00353 P81846, Citropin GLFDIIKKVASVIGGL 2164 1.3 (amphibian, frog) AP00338 P81903, Histone PDPAKTAPKKGSKKAVTKA 2165 H2B-1(HLP-1) (fish) AP00271 P82018, ChBac5 RFRPPIRRPPIRPPFNPPFRPPVRPPF 2166 (Goat cathelicidin) RPPFRPPFRPPIGPFP AP00316 P82027, Uperin 2.1 GIVDFAKKVVGGIRNALGI 2167 (amphibian, toad) AP00317 P82028, Uperin 2.2 GFVDLAKKVVGGIRNAL GI 2168 (amphibian, toad) AP00318 P82029, Uperin 2.3 GFFDLAKKVVGGIRNALGI 2169 (amphibian, toad) AP00319 P82030, Uperin 2.4 GILDFAKTVVGGIRNAL GI 2170 (amphibian, toad) AP00320 P82031, Uperin 2.5 GIVDFAKGVLGKIKNVLGI 2171 (amphibian, toad) AP00323 P82032, Uperin 3.1 GVLDAFRKIATVVKNVV 2172 (amphibian, toad) AP00326 P82035, Uperin 4.1 GVGSFIHKVVSAIKNVA 2173 (amphibian, toad) AP00321 P82039, Uperin 2.7 GIIDIAKKLVGGIRNVLGI 2174 (amphibian, toad) AP00322 P82040, Uperin 2.8 GILDVAKTLVGKLRNVLGI 2175 (amphibian, toad) AP00324 P82042, Uperin 3.5 GVGDLIRKAVSVIKNIV 2176 (amphibian, toad) AP00325 P82042, Uperin 3.6 GVIDAAKKVVNVLKNLP 2177 (amphibian, toad) AP00327 P82050, Uperin 7.1 GWFDVVKHIASAV 2178 (amphibian, frog) AP00260 P82066, Maculatin GLFVGVLAKVAAHVVPAIAEHF 2179 1.1 (XXA, frog, ZZHa) AP00261 P82067, Maculatin GLFVGLAKVAAHNNPAIAEHFQA 2180 1.2 (XXA, frog) AP00262 P82068, Maculatin GFVDFLKKVAGTIANVVT 2181 2.1 (frog) AP00263 P82069, Maculatin GLLQTIKEKLESLESLAKGIVSGIQ 2182 3.1 (frog) A AP00345 P82104, Caerin GLLSVLGSVAKHVLPHVVPVIAEK 2183 1.10 (frog) L AP00456 P82232, Brevinin- VNPIILGVLPKFVCLITKKC 2184 1T (frog) AP00459 P82233, Brevinin- FITLLLRKFICSITKKC 2185 1TA (frog) AP00457 P82234, Brevinin- GLWETIKNFGKKFTLNILHKLKCKI 2186 2TC (frog) GGGC AP00458 P82235, Brevinin- GLWETIKNFGKKFTLNILHNLKCKI 2187 2TD (frog) GGGC AP00397 P82238, SGFVLKGYTKTSQ 2188 Salmocidin 2A (fish, trout) AP00398 P82239, AGFVLKGYTKTSQ 2189 Salmocidin 2B (fish, trout) AP00055 P82282, Bombinin IIGPVLGMVGSALGGLLKKI 2190 H1 (frog) AP00056 P82284, Bombinin LIGPVLGLVGSALGGLLKKI 2191 H4 (frog, XXA, XXD) AP00057 P82285, Bombinin IIGPVLGLVGSALGGLLKKI 2192 H5 (frog, XXD) AP00419 P82286, Bombinin- GIGASILSAGKSALKGFAKGLAEHF 2193 like peptides 2 AN (amphibian, toad) AP00137 P82293, Cryptdin-1 LRDLVCYCRTRGCKRRERMNGTC 2194 (Crp1, animal RKGHLMYTLCCR defensin, alpha, mouse) AP00443 P82317, defensin ACYCRIPACLAGERRYGTCFYMGR 2195 RMAD-2 (monkey) VWAFCC AP00012 P82386, Aurein 1.1 GLFDIIKKIAESI 2196 (amphibian, frog) AP00014 P82388, Aurein 2.1 GLLDIVKKVVGAFGSL 2197 (amphibian, frog) AP00015 P82389, Aurein 2.2 GLFDIVKKVVGALGSL 2198 (amphibian, frog) AP00016 P82390, Aurein 2.3 GLFDIVKKVVGAIGSL 2199 (XXA, amphibian, frog) AP00017 P82391, Aurein 2.4 GLFDIVKKVVGTIAGL 2200 (XXA, amphibian, frog) AP00018 P82392, Aurein 2.5 GLFDIVKKVVGAFGSL 2201 (XXA, amphibian, frog) AP00019 P82393, Aurein 2.6 GLFDIAKKVIGVIGSL 2202 (XXA, amphibian, frog) AP00020 P82394, Aurein 3.1 GLFDIVKKIAGHIAGSI 2203 (XXA, amphibian, frog) AP00021 P82395, Aurein 3.2 GLFDIVKKIAGHIASSI 2204 (XXA, amphibian, frog) AP00022 P82396, Aurein 3.3 GLFDIVKKIAGHIVSSI 2205 (XXA, amphibian, frog) AP00376 P82414, Ponericin GWKDWAKKAGGWLKKKGPGMA 2206 G1 (ants) KAALKAAMQ AP00377 P82415, Ponericin GWKDWLKKGKEWLKAKGPGIVK 2207 G2 (ants) AALQAATQ AP00378 P82416, Ponericin GWKDWLNKGKEWLKKKGPGIMK 2208 G3 (ants) AALKAATQ AP00379 P82417, Ponericin DFKDWMKTAGEWLKKKGPGILKA 2209 G4 (ants) AMAAAT AP00380 P82418, Ponericin GLKDWVKIAGGWLKKKGPGILKA 2210 G5 (ants) AMAAATQ AP00381 P82419, Ponericin GLVDVLGKVGGLIKKLLP 2211 G6 (ants) AP00382 P82420, Ponericin GLVDVLGKVGGLIKKLLPG 2212 G7 (ants) AP00383 P82421, Ponericin LLKELWTKMKGAGKAVLGKIKGL 2213 L1 (ants) L AP00384 P82422, Ponericin LLKELWTKIKGAGKAVLGKIKGLL 2214 L2 (ants) AP00386 P82423, Ponericin WLGSALKIGAKLLPSVVGLFKKKK 2215 W1 (ants) Q AP00387 P82424, Ponericin WLGSALKIGAKLLPSVVGLFQKKK 2216 W2 (ants) K AP00388 P82425, Ponericin GIWGTLAKIGIKAVPRVISMLKKK 2217 W3 (ants) KQ AP00389 P82426, Ponericin GIWGTALKWGVKLLPKLVGMAQT 2218 W4 (ants) KKQ AP00390 P82427, Ponericin FWGALIKGAAKLIPSVVGLFKKKQ 2219 W5 (ants) AP00391 P82428, Ponericin FIGTALGIASAIPAIVKLFK 2220 W6 (ants) AP00303 P82651, Tigerinin- FCTMIPIPRCY 2221 1 (frog) AP00304 P82652, Tigerinin- RVCFAIPLPICH 2222 2 (frog) AP00305 P82653, Tigerinin- RVCYAIPLPICY 2223 3 (frog) AP00301 P82656, Hadrurin GILDTIKSIASKVWNSKTVQDLKR 2224 (scorpion) KGINWVANKLGVSPQAA AP00113 P82740, GLLSGLKKVGKHVAKNVAVSLMD 2225 RANATUERIN 1T SLKCKISGDC (frog) AP00114 P82741, SMLSVLKNLGKVGLGFVACKINK 2226 RANATUERIN 1 QC (Ranatuerin-1, frog) AP00115 P82742, GLFLDTLKGAAKDVAGKLEGLKC 2227 RANATUERIN 2 KITGCKLP (Ranatuerin-2, frog) AP00116 P82780, GFLDIINKLGKTFAGHMLDKIKCTI 2228 RANATUERIN 3 GTCPPSP (Ranatuerin-3, frog) AP00117 P82819, FLPFIARLAAKVFPSIICSVTKKC 2229 RANATUERIN 4 (Ranatuerin-4, frog) AP00405 P82821, FISAIASMLGKFL 2230 RANATUERIN 6 (frog) AP00406 P82822, FLSAIASMLGKFL 2231 RANATUERIN 7 (frog) AP00407 P82823, FISAIASFLGKFL 2232 RANATUERIN 8 (frog) AP00408 P82824, FLFPLITSFLSKVL 2233 RANATUERIN 9 (frog) AP00461 P82825, Brevinin- FLPMLAGLAASMVPKLVCLITKKC 2234 1LA (frog) AP00462 P82826, Brevinin- FLPMLAGLAASMVPKFVCLITKKC 2235 1LB (frog) AP00118 P82828, GILDSFKGVAKGVAKDLAGKLLD 2236 RANATUERIN KLKCKITGC 2La (Ranatuerin- 2La, frog) AP00119 P82829, GILSSIKGVAKGVAKNVAAQLLDT 2237 RANATUERIN LKCKITGC 2Lb (Ranatuerin- 2Lb, frog) AP00109 P82830, Temporin-  VLPLISMALGKLL 2238 1La (Temporin 1La, frog) AP00110 P82831, Temporin- NFLGTLINLAKKIM 2239 1Lb (Temporin 1Lb, frog) AP00111 P82832, Temporin- FLPILINLIHKGLL 2240 1Lc (Temporin 1Lc, frog) AP00463 P82833, Brevinin- FLPFIAGMAAKFLPKIFCAISKKC 2241 1BA (frog) AP00464 P82834, Brevinin- FLPAIAGMAAKFLPKIFCAISKKC 2242 1BB (frog) AP00465 P82835, Brevinin- FLPFIAGVAAKFLPKIFCAISKKC 2243 1BC (frog) AP00466 P82836, Brevinin- FLPAIAGVAAKFLPKIFCAISKKC 2244 1BD (frog) AP00467 P82837, Brevinin- FLPAIVGAAAKFLPKIFCVISKKC 2245 1BE (frog) AP00468 P82838, Brevinin- FLPFIAGMAANFLPKIFCAISKKC 2246 1BF (frog) AP00120 P82840, GLLDTIKGVAKTVAASMLDKLKC 2247 RANATUERIN 2B KISGC (Ranatuerin-2B, frog) AP00469 P82841, Brevinin- FLPIIAGVAAKVFPKIFCAISKKC 2248 1PA (frog) AP00460 P82842, Brevinin- FLPIIAGIAAKVFPKIFCAISKKC 2249 1PB (frog) AP00470 P82843, Brevinin- FLPIIASVAAKVFSKIFCAISKKC 2250 1PC (frog) AP00471 P82844, Brevinin- FLPIIASVAANVFSKIFCAISKKC 2251 1PD (frog) AP00472 P82845, Brevinin- FLPIIASVAAKVFPKIFCAISKKC 2252 1PE (frog) AP00121 P82847, GLMDTVKNVAKNLAGHMLDKLK 2253 RANATUERIN 2P CKITGC (Ranatuerin-2P, frog) AP00112 P82848, Temporin- FLPIVGKLLSGLL 2254 1P (Temporin 1P, frog) AP00452 P82871, Brevinin- FLPVVAGLAAKVLPSIICAVTKKC 2255 1SY (frog) AP00122 P82875, SMLSVLKNLGKVGLGLVACKINK 2256 Ranatuerin-1C QC (Ranatuerin 1C, frog) AP00514 P82876, Ranalexin- FLGGLMKAFPALICAVTKKC 2257 1Ca (frog) AP00515 P82877, Ranalexin- FLGGLMKAFPAIICAVTKKC 2258 1Cb (frog) AP00124 P82878, GLFLDTLKGAAKDVAGKLLEGLK 2259 Ranatuerin-2Ca CKIAGCKP (Ranatuerin 2Ca, frog) AP00123 P82879, GLFLDTLKGLAGKLLQGLKCIKAG 2260 Ranatuerin-2Cb CKP (Ranatuerin 2Cb, frog) AP00104 P82880, Temporin- FLPFLAKILTGVL 2261 1Ca (Temporin 1Ca, frog) AP00105 P82881, Temporin- FLPLFASLIGKLL 2262 1Cb (Temporin 1Cb, frog) AP00106 P82882, Temporin- FLPFLASLLTKVL 2263 1Cc (Temporin 1Cc, frog) AP00107 P82883, Temporin- FLPFLASLLSKVL 2264 1Cd (Temporin 1Cd, frog) AP00108 P82884, Temporin- FLPFLATLLSKVL 2265 1Ce (Temporin 1Ce, frog) AP00453 P82904, Brevinin- FLPAIVGAAGQFLPKIFCAISKKC 2266 1SA (frog) AP00454 P82905, Brevinin- FLPAIVGAAGKFLPKIFCAISKKC 2267 1SB (frog) AP00455 P82906, Brevinin- FFPIVAGVAGQVLKKIYCTISKKC 2268 1SC (frog) AP00996 P82907, Lichenin ISLEICAIFHDN 2269 (bacteria) AP00302 P82951, Hepcidin GCRFCCNCCPNMSGCGVCCRF 2270 (fish) AP00058 P83080, Maximin 1 GIGTKILGGVKTALKGALKELAST 2271 (toad) YAN AP00059 P83081, Maximin 2 GIGTKILGGVKTALKGALKELAST 2272 (toad) YVN AP00060 P83082, Maximin 3 GIGGKILSGLKTALKGAAKELAST 2273 (toad, ZZHa) YLH AP00061 P83083, Maximin 4 GIGGVLLSAGKAALKGLAKVLAE 2274 (toad) KYAN AP00062 P83084, Maximin 5 SIGAKILGGVKTFFKGALKELASTY 2275 (toad) LQ AP00063 P83085, Maximin 6 ILGPVISTIGGVLGGLLKNL 2276 (toad) AP00064 P83086, Maximin 7 ILGPVLGLVGNALGGLIKNE 2277 (toad) AP00065 P83087, Maximin 8 ILGPVLSLVGNALGGLLKNE 2278 (toad) AP00355 P83171, ANTAFVSSAHNTQKIPAGAPFNRN 2279 Ginkbilobin LRAMLADLRQNAAFAG (Chinese plant) AP00475 P83188, Pseudin 1 GLNTLKKVFQGLHEAIKLINNHVQ 2280 (frog) AP00476 P83189, Pseudin 2 GLNALKKVFQGIHEAIKLINNHVQ 2281 (frog) AP00477 P83190, Pseudin 3 GINTLKKVIQGLHEVIKLVSNHE 2282 (frog) AP00478 P83191, Pseudin 4 GINTLKKVIQGLHEVIKLVSNHA 2283 (frog) AP00410 P83287, SKGKKANKDVELARG 2284 Oncorhyncin III (fish) AP00357 P83305, Japonicin- FFPIGVFCKIFKTC 2285 1 (amphibian, frog) AP00358 P83306, Japonicin- FGLPMLSILPKALCILLKRKC 2286 2 (amphibian, frog) AP00385 P83312, FKLGSFLKKAWKSKLAKKLRAKG 2287 Parabutoporin KEMLKDYAKGLLEGGSEEVPGQ (scorpion) AP00374 P83313, GKVWDWIKSTAKKLWNSEPVKEL 2288 Opistoporin 1 KNTALNAAKNLVAEKIGATPS (scorpion) AP00375 P83314, GKVWDWIKSTAKKLWNSEPVKEL 2289 Opistoporin 2 KNTALNAAKNFVAEKIGATPS (scorpion) AP00336 P83327, Histone AERVGAGAPVYL 2290 H2A (fish) AP00335 P83338, Histone PKRKSATKGDEPA 2291 H6-like protein (fish) AP00411 P83374, KAVAAKKSPKKAKKPAT 2292 Oncorhyncin II (fish) AP00999 P83375, Serracin-P DYHHGVRVL 2293 43 kDa subunit (bacteria) AP00284 P83376, SHQDCYEALHKCMASHSKPFSCS 2294 Dolabellanin B2 MKFHMCLQQQ (sea hare) AP00998 P83378, Serracin-P ALPKKLKYLNLFNDGFNYMGVV 2295 23 kDa subunit (bacteriocin, bacteria) AP00129 P83403, Cecropin GWLKKIGKKIERVGQNTRDATVK 2296 (insect, moth) GLEVAQQAANVAATVR AP00127 P83413, Cecropin RWKVFKKIEKVGRNIRDGVIKAAP 2297 A (insect, moth) AIEVLGQAKAL AP00372 P83416, Virescein GKIPIGAIKKAGKAIGKGLRAVNIA 2298 (insect) STAHDVYTFFKPKKRH AP00356 P83427, Heliocin QRFIHPTYRPPPQPRRPVIMRA 2299 (insect) AP00409 P83428, Locustin ATTGCSCPQCIIFDPICASSYKNGRR 2300 (insect) GFSSGCHMRCYNRCHGTDYFQISK GSKCI AP00339 P83545, FFGWLIKGAIHAGKAIHGLIHRRRH 2301 Chrysophsin-1 (Red sea bream, madai) AP00340 P83546, FFGWLIRGAIHAGKAIHGLIHRRRH 2302 Chrysophsin-2 (Red sea bream, madai) AP00341 P83547, FIGLLISAGKAIHDLIRRRH 2303 Chrysophsin-3 (Red sea bream, madai) AP01004 P84763, Thuricin-S DWTAWSALVAAACSVELL 2304 (bacteria) AP00553 P84868, Sesquin KTCENLADTY 2305 (plant, ZZHp) AP00132 Q06589, Cecropin GWLKKIGKKIERVGQHTRDATIQTI 2306 1 (insect, fly) AVAQQAANVAATAR AP00135 Q06590, Cecropin GWLKKIGKKIERVGQHTRDATIQTI 2307 2 (insect fly) GVAQQAANVAATLK AP00416 Q17313, SLGGVISGAKKVAKVAIPIGKAVLP 2308 Ceratotoxin C VVAKLVG (insect, fly) AP00171 Q24395, HRHQGPIFDTRPSPFNPNQPRPGPIY 2309 Metchnikowin (insect) AP00354 Q27023, Tenecin 1 VTCDILSVEAKGVKLNDAACAAH 2310 (insect) CLFRGRSGGYCNGKRVCVCR AP00401 Q28880, Lingual GFTQGVRNSQSCRRNKGICVPIRCP 2311 antimicrobial GSMRQIGTCLGAQVKCCRRK peptide (LAP, beta defensin, cow) AP00224 Q62713, RatNP-3 CSCRTSSCRFGERLSGACRLNGRIY 2312 (rat) RLCC AP00225 Q62714, RatNP-4 ACYCRIGACVSGERLTGACGLNGR 2313 (rat) IYRLCCR AP00223 Q62715, RatNP-2 VTCYCRSTRCGFRERLSGACGYRG 2314 (rat) RIYRLCCR AP00222 Q62716, RatNP-1 VTCYCRRTRCGFRERLSGACGYRG 2315 (rat) RIYRLCCR AP00174 Q64365, GNCP-1 RRCICTTRTCRFPYRRLGTCIFQNR 2316 (Guinea pig VYTFCC neutrophil cationic peptide 1) AP00311 Q90W78, Galensin CYSAAKYPGFQEFINRKYKSSRF 2317 (frog) AP00395 Q95NT0, HSSGYTRPLPKPSRPIFIRPIGCDVC 2318 Penaeidin-4a YGIPSSTARLCCFRYGDCCHR (shrimp, Crustacea) AP00423 Q962B0, QGYKGPYTRPILRPYVRPVVSYNA 2319 Penaeidin-3n CTLSCRGITTTQARSCSTRLGRCCH (shrimp, Crustacea) VAKGYS AP00422 Q962B1, QGCKGPYTRPILRPYVRPVVSYNA 2320 Penaeidin-3m CTLSCRGITTTQARSCCTRLGRCCH (shrimp, Crustacea) VAKGYS AP00421 Q963C3, YSSGYTRPLPKPSRPIFIRPIGCDVC 2321 Penaeidin-4C YGIPSSTARLCCFRYGDCCHR (shrimp, Crustacea) AP00210 Q99134, PGLa GMASKAGAIAGKIAKVALKAL 2322 (African clawed frog, XXA) AP00054 Q9DET7, GIGGALLSAGKSALKGLAKGLAEH 2323 Bombinin-like FAN peptide 7 (BLP-7, toad) AP00315 Q9PT75, SLGSFLKGVGTTLASVGKVVSDQF 2324 Dermatoxin (Two- GKLLQAGQ colored leaf frog) AP00133 Q9Y0Y0, Cecropin GGLKKLGKKLEGVGKRVFKASEK 2325 B (insect, ALPVLTGYKAIG mosquito) AP00004 Ref, Ct-AMP1 NLCERASLTWTGNCGNTGHCDTQ 2326 (CtAMP1, C. CRNWESAKHGACHKRGNWKCFC ternatea- YFDC antimicrobial peptide 1, plant defensin) AP00027 Ref, hexapeptide RRWQWR 2327 (synthetic) AP00529 Ref, Lantibiotic WKSESVCTPGCVTGVLQTCFLQTI 2328 Ericin S (bacteria) TCNCHISK AP00306 Ref, Tigerinin-4 RVCYAIPLPIC 2329 (frog) AP00309 Ref, Human KS-27 KSKEKIGKEFKRIVQRIKDFLRNLV 2330 (KS27 from LL-37) PR AP00344 Ref, Apidaecin II GNNRPIYIPQPRPPHPRL 2331 (honeybee, insect) AP00424 Ref, XT1 (frog) GFLGPLLKLAAKGVAKVIPHLIPSR 2332 QQ AP00425 Ref, XT 2 (frog) GCWSTVLGGLKKFAKGGLEAIVNP 2333 K AP00426 Ref, XT 4 (frog) GVFLDALKKFAKGGMNAVLNPK 2334 AP00427 Ref, XT 7 (frog) GLLGPLLKIAAKVGSNLL 2335 AP00431 Ref, human LLP 1 RVIEVVQGACRAIRHIPRRIRQGLE 2336 RIL AP00432 Ref, human LLP RIAGYGLRGLAVIIRICIRGLNLIFEI 2337 IR AP00447 Ref, Anoplin GLLKRIKTLL 2338 (insect) AP00474 Ref, Piscidin 3 FIHHIFRGIVHAGRSIGRFLTG 2339 (fish) AP00481 Ref, Kaliocin-1 FFSASCVPGADKGQFPNLCRLCAG 2340 (synthetic) TGENKCA AP00482 Ref, Thionin KSCCRNTWARNCYNVCRLPGTISR 2341 mutation EICAKKCRCKIISGTTCPSDYPK (synthetic) AP00484 Ref, Stomoxyn RGFRKHFNKLVKKVKHTISETAHV 2342 (insect, fly) AKDTAVIAGSGAAVVAAT AP00486 Ref, Cupiennin 1b GFGSLFKFLAKKVAKTVAKQAAK 2343 (spider) QGAKYIANKQME AP00487 Ref, Cupiennin 1c GFGSLFKFLAKKVAKTVAKQAAK 2344 (spider) QGAKYIANKQTE AP00488 Ref, Cupiennin 1D GFGSLFKFLAKKVAKTVAKQAAK 2345 (spider) QGAKYVANKHME AP00489 Ref, Hipposin SGRGKTGGKARAKAKTRS SRAGL 2346 (fish) QFPVGRVHRLLRKGNYAHRVGAG APVYL AP00923 Ref, AISYGNGVYCNKEKCWVNKAENK 2347 Carnobacteriocin QAITGIVIGGWASSLAGMGH B1 (XXO, class IIa bacteriocin, bacteria) AP00496 Ref, HP 2-20 AKKVFKRLEKLFSKIQNDK 2348 (synthetic) AP00497 Ref, Maximin H5 ILGPVLGLVSDTLDDVLGIL 2349 (toad) AP00498 Ref, rCRAMP (rat GLVRKGGEKFGEKLRKIGQKIKEF 2350 cathelicidin) FQKLALEIEQ AP00500 Ref, S9-P18 KWKLFKKISKFLHLAKKF 2351 (synthetic) AP00501 Ref, L9-P18 KWKLFKKILKFLHLAKKF 2352 (synthetic) AP00502 Ref, Clavaspirin FLRFIGSVIHGIGHLVHHIGVAL 2353 (sea squirt, tunicate) AP00503 Ref, human P- AKRHHGYKRKFH 2354 113D AP00504 Ref, human MUC7 LAHQKPFIRKSYKCLHKRCR 2355 20-Mer AP00507 Ref, Nigrocin 2 GLLSKVLGVGKKVLCGVSGLC 2356 (frog) AP00508 Ref, Nigrocin 1 GLLDSIKGMAISAGKGALQNLLKV 2357 (frog) ASCKLDKTC AP00509 Ref, human VAIALKAAHYHTHKE 2358 Calcitermin AP00510 Ref, Dicynthaurin ILQKAVLDCLKAAGSSLSKAAITAI 2359 (sea peach) YNKIT AP00511 Ref, KIGAKI KIGAKIKIGAKIKIGAKI 2360 (synthetic) AP00516 Ref, Lycotoxin I IWLTALKFLGKHAAKHLAKQQLS 2361 (spider) KL AP00517 Ref, Lycotoxin II KIKWFKTMKSIAKFIAKEQMKKHL 2362 (spider) GGE AP00518 Ref, Ib-AMP3 QYRHRCCAWGPGRKYCKRWC 2363 (plant defensin, balsam) AP00519 Ref, Ib-AMP4 EWGRRCCGWGPGRRYCRRWC 2364 (plant defensin, balsam) AP00521 Ref, Dhvar4 KRLFKKLLFSLRKY 2365 (synthetic) AP00522 Ref, Dhvar5 LLLFLLKKRKKRKY 2366 (synthetic) AP00525 Ref, Maximin H2 ILGPVLSMVGSALGGLIKKI 2367 (toad) AP00526 Ref, Maximin H3 ILGPVLGLVGNALGGLIKKI 2368 (toad) AP00527 Ref, Maximin H4 ILGPVISKIGGVLGGLLKNL 2369 (toad) AP00528 Ref, Anionic DDDDDD 2370 peptide SAAP (sheep) AP00530 Ref, Lantibiotic VLSKSLCTPGCITGPLQTCYLCFPT 2371 Ericin_A (bacteria)  FAKC AP00531 Ref, Kenojeinin I GKQYFPKVGGRLSGKAPLAAKTH 2372 (sea skate) RRLKP AP00532 Ref, Lunatusin KTCENLADTFRGPCFATSNC 2373 (plant, ZZHp) AP00533 Ref, Fallaxin (frog) GVVDILKGAAKDIAGHLASKVMN 2374 KL AP00534 Ref, Tu-AMP 2 KSCCRNTTARNCYNVCRIPG 2375 (TuAMP2, thionin- like antimicrobial peptides, plant defensin, tulip) AP00535 Ref, Pilosulin 1 GLGSVFGRLARILGRVIPKVAKKL 2376 (Myr b I) GPKVAKVLPKVMKEAIPMAVEMA (Australian ants) KSQEEQQPQ AP00536 Ref, Luxuriosin SVRTQDNAVNRQIFGSNGPYRDFQ 2377 (insect) LSDCYLPLETNPYCNEWQFAYHW NNALMDCERAIYHGCNRTRNNFIT LTACKNQAGPICNRRRH AP00537 Ref, SAMP H1 AEVAPAPAAAAPAKAPKKKAAAK 2378 (fish, Atlantic PKKAGPS salmon) AP00538 Ref, Halocidin WLNALLHHGLNCAKGVLA 2379 (dimer Hal18 + Hal15)(tunicate) AP00539 Ref, AOD GFGCPWNRYQCHSHCRSIGRLGGY 2380 (American oyster CAGSLRLTCTCYRS defensin, animal defensin) AP00540 Ref, Pentadactylin GLLDTLKGAAKNVVGSLASKVME 2381 (frog) KL AP00541 Ref, Polybia-MPI IDWKKLLDAAKQIL 2382 (insect, social wasp) AP00542 Ref, Polybia-CP ILGTILGLLKSL 2383 (insect, social wasp) AP00543 Ref, Ocellatin-1 GVVDILKGAGKDLLAHLVGKISEK 2384 (XXA, frog) V AP00544 Ref, Ocellatin-2 GVLDIFKDAAKQILAHAAEKQI 2385 (XXA, frog) AP00545 Ref, Ocellatin-3 GVLDILKNAAKNILAHAAEQI 2386 (frog) AP00548 Ref, CMAP 27 RFGRFLRKIRRFRPKVTITIQGSARF 2387 (chicken myeloid G antimicrobial peptide 27, bird cathelicidin, chicken cathelicidin) AP00550 Ref, Tu-AMP-1 KSCCRNTVARNCYNVCRIPGTPRP 2388 (TuAMP1, thionin- VCAATCDCKLITGTKCPPGYEK like antimicrobial peptides, plant defensin, tulip) AP00551 Ref, Combi-2 FRWWHR 2389 (synthetic) AP00552 Ref, Maximin 9 GIGRKFLGGVKTTFRCGVKDFASK 2390 (frog) HLY AP00554 Ref, S1 moricin GKIPVKAIKKAGAAIGKGLRAINIA 2391 (insect) STAHDVYSFFKPKHKKK AP00555 Ref, Parasin I KGRGKQGGKVRAKAKTRSS 2392 (catfish) AP00556 Ref, Kassinatuerin- GFMKYIGPLIPHAVKAISDLI 2393 1 (frog) AP00557 Ref, Fowlicidin-1 RVKRVWPLVIRTVIAGYNLYRAIK 2394 (chCATH-1, bird KK cathelicidin, chicken cathelicidin) AP00559 Ref, Eryngin ATRVVYCNRRSGSVVGGDDTVYY 2395 (mushroom, fungi) EG AP00560 Ref, Dendrocin TTLTLHNLCPYPVWWLVTPNNGG 2396 (plant, bamboo) FPIIDNTPVVLG AP00561 Ref, Coconut EQCREEEDDR 2397 antifungal peptide (plant) AP00562 Ref, Pandinin 1 GKVWDWIKSAAKKIWSSEPVSQL 2398 (African scorpion) KGQVLNAAKNYVAEKIGATPT AP00563 Ref, White cloud KTCENLADTFRGPCFATSNCDDHC 2399 bean defensin KNKEHLLSGRCRDDFRCWCTRNC (plant defensin) AP00564 Ref, Dybowskin-1 FLIGMTHGLICLISRKC 2400 (frog) AP00565 Ref, Dybowskin-2 FLIGMTQGLICLITRKC 2401 (frog) AP00566 Ref, Dybowskin-3 GLFDVVKGVLKGVGKNVAGSLLE 2402 (frog) QLKCKLSGGC AP00567 Ref, Dybowskin-4 VWPLGLVICKALKIC 2403 (frog) AP00568 Ref, Dybowskin-5 GLFSVVTGVLKAVGKNVAKNVGG 2404 (frog) SLLEQLKCKKISGGC AP00569 Ref, Dybowskin-6 FLPLLLAGLPLKLCFLFKKC 2405 (frog) AP00570 Ref, Pleurain-A1 SIITMTKEAKLPQLWKQIACRLYNT 2406 (frog) C AP00571 Ref, Pleurain-A2 SIITMTKEAKLPQSWKQIACRLYNT 2407 (frog) C AP00574 Ref, Esculentin- GLFSKFAGKGIKNLIFKGVKHIGKE 2408 IGRa (frog) VGMDVIRTGIDVAGCKIKGEC AP00575 Ref, Brevinin- GLLDTFKNLALNAAKSAGVSVLNS 2409 2GRa (frog) LSCKLSKTC AP00576 Ref, Brevinin- GVLGTVKNLLIGAGKSAAQSVLKT 2410 2GRb (frog) LSCKLSNDC AP00577 Ref, Brevinin- GLFTLIKGAAKLIGKTVAKEAGKT 2411 2GRc (frog) GLELMACKITNQC AP00578 Ref, Brevinin- FLPLLAGLAANFLPKIFCKITKKC 2412 1GRa (frog) AP00579 Ref, Nigrocin- GLLSGILGAGKHIVCGLSGLC 2413 2GRa (frog) AP00580 Ref, Nigrocin- GLFGKILGVGKKVLCGLSGMC 2414 2GRb (frog) AP00581 Ref, Nigrocin- GLLSGILGAGKNIVCGLSGLC 2415 2GRc (frog) AP00582 Ref, Brevinin- GFSSLFKAGAKYLLKSVGKAGAQ 2416 2GHa (frog) QLACKAANNCA AP00583 Ref, Brevinin- GVITDALKGAAKTVAAELLRKAH 2417 2GHb (frog) CKLTNSC AP00584 Ref, Guentherin VIDDLKKVAKKVRRELLCKKHHK 2418 (frog) KLN AP00585 Ref, Brevinin- SIWEGIKNAGKGFLVSILDKVRCK 2419 2GHc (frog) VAGGCNP AP00586 Ref, Temporin-GH FLPLLFGAISHLL 2420 (frog) AP00587 Ref, Brevinin-2TSa GIMSLFKGVLKTAGKHVAGSLVD 2421 (frog) QLKCKITGGC AP00588 Ref, Brevinin-1TSa FLGSIVGALASALPSLISKIRN 2422 (frog) AP00589 Ref, Temporin- FLGALAKIISGIF 2423 1TSa (frog) AP00593 Ref, Brevinin-1CSa FLPILAGLAAKIVPKLFCLATKKC 2424 (frog) AP00594 Ref, Temporin- FLPIVGKLLSGLL 2425 1CSa (frog) AP00595 Ref, Temporin- FLPIIGKLLSGLL 2426 1CSb (frog) AP00596 Ref, Temporin- FLPLVTGLLSGLL 2427 1CSc (frog) AP00597 Ref, Temporin- NFLGTLVNLAKKIL 2428 1CSd (frog) AP00598 Ref, Temporin- FLSAITSLLGKLL 2429 1SPb (frog) AP00599 Ref, Brevinin-2- GIWDTIKSMGKVFAGKILQNL 2430 related (frog) AP00600 Ref, Odorranain- GLLRASSVWGRKYYVDLAGCAKA 2431 HP (frog) AP00601 Ref, Brevinin- FLSLALAALPKFLCLVFKKC 2432 1DYa (frog) AP00602 Ref, Brevinin- FLSLALAALPKLFCLIFKKC 2433 1DYb (frog) AP00603 Ref, Brevinin- FLPLLLAGLPKLLCLFFKKC 2434 1DYc (frog) AP00607 Ref, Brevinin- GLFDVVKGVLKGAGKNVAGSLLE 2435 2DYb (frog) QLKCKLSGGC AP00608 Ref, Brevinin- GLFDVVKGVLKGVGKNVAGSLLE 2436 2DYc (frog) QLKCKLSGGC AP00609 Ref, Brevinin- GIFDVVKGVLKGVGKNVAGSLLE 2437 2DYd (frog) QLKCKLSGGC AP00610 Ref, Brevinin- GLFSVVTGVLKAVGKNVAKNVGG 2438 2DYe (frog) SLLEQLKCKISGGC AP00611 Ref, Temporin- FIGPIISALASLFG 2439 1DYa (frog) AP00615 Ref, Palustrin-1b ALFSILRGLKKLGNMGQAFVNCKI 2440 (frog) YKKC AP00616 Ref, Palustrin-1c ALSILRGLEKLAKMGIALTNCKAT 2441 (frog) KKC AP00617 Ref, Palustrin-1d ALSILKGLEKLAKMGIALTNCKAT 2442 (frog) KKC AP00619 Ref, Palustrin-2b GFFSTVKNLATNVAGTVIDTLKCK 2443 (frog) VTGGCRS AP00620 Ref, Palustrin-2c GFLSTVKNLATNVAGTVIDTLKCK 2444 (frog) VTGGCRS AP00621 Ref, Palustrin-3a GIFPKIIGKGIKTGIVNGIKSLVKGV 2445 (frog) GMKVFKAGLNNIGNTGCNEDEC AP00622 Ref, Palustrin-3b GIFPKIIGKGIKTGIVNGIKSLVKGV 2446 (frog) GMKVFKAGLSNIGNTGCNEDEC AP00624 Ref, human ALL- ALLGDFFRKSKEKIGKEFKRIVQRI 2447 38 (an LL-37 KDFLRNLVPRTES analog released from its precursor hCAP-18 by gastricsin in vivo) AP00625 Ref, human KR-20 KRIVQRIKDFLRNLVPRTES 2448 (KR20 from LL- 37) AP00626 Ref, human KS-30 KSKEKIGKEFKRIVQRIKDFLRNLV 2449 (KS30 from LL-37) PRTES AP00627 Ref, human RK-31 RKSKEKIGKEFKRIVQRIKDFLRNL 2450 (RK31 from LL- VPRTES 37) AP00628 Ref, human LL-23 LLGDFFRKSKEKIGKEFKRIVQR 2451 (LL23 from LL-37) AP00629 Ref, human LL-29 LLGDFFRKSKEKIGKEFKRIVQRIK 2452 (LL29 from LL-37) DFLR AP00630 Ref, Amoeba GEILCNLCTGLINTLENLLTTKGAD 2453 peptide (protozoan para AP00631 Ref, Mundticin KYYGNGVSCNKKGCSVDWGKAIG 2454 (bacteria) IIGNNSAANLATGGAAGWSK AP00638 Ref, Citropin 2.1 GLIGSIGKALGGLLVDVLKPKL 2455 (frog) AP00639 Ref, Citropin 2.1.3 GLIGSIGKALGGLLVDVLKPKLQA 2456 (frog) AS AP00640 Ref, Maculatin 1.3 GLLGLLGSVVSHVVPAIVGHF 2457 (frog) AP00641 Ref, Pardaxin 1 GFFALIPKIISSPLFKTLLSAVGSALS 2458 (Pardaxin P-1, SSGEQE Pardaxin P1, Pa1, flat fish) AP00642 Ref, Pardaxin 2 GFFALIPKIISSPIFKTLLSAVGSALS 2459 (Pardaxin P-2, SSGGQE Pardaxin P2, Pa2, flat fish) AP00643 Ref, Pardaxin 3 GFFAFIPKIISSPLFKTLLSAVGSALS 2460 (Pardaxin P-3, SSGEQE Pardaxin P3, Pa3, flat fish) AP00645 Ref, Pardaxin 5 GFFAFIPKIISSPLFKTLLSAVGSALS 2461 (Pardaxin P-5, SSGDQE Pardaxin P5, Pa5, flat fish) AP00647 Ref, Brevinin-1PLb FLPLIAGLAANFLPKIFCAITKKC 2462 (frog) AP00648 Ref, Brevinin-1PLc FLPVIAGVAAKFLPKIFCAITKKC 2463 (frog) AP00649 Ref, Esculentin- GLFPKINKKKAKTGVFNIIKTVGKE 2464 1PLa (frog) AGMDLIRTGIDTIGCKIKGEC AP00650 Ref, Esculentin- GIFTKINKKKAKTGVFNIIKTIGKEA 2465 1PLb (frog) GMDVIRAGIDTISCKIKGEC AP00651 Ref, Esculentin- GLFSILKGVGKIALKGLAKNMGK 2466 2PLa (frog) MGLDLVSCKISKEC AP00652 Ref, Ranatuerin- GIMDTVKNVAKNLAGQLLDKLKC 2467 2PLa (frog) KITAC AP00653 Ref, Ranatuerin- GIMDTVKNAAKDLAGQLLDKLKC 2468 2PLb (frog) RITGC AP00654 Ref, Ranatuerin- GLLDTIKNTAKNLAVGLLDKIKCK 2469 2PLc (frog) MTGC AP00655 Ref, Ranatuerin- GIMDSVKNVAKNIAGQLLDKLKC 2470 2PLd (frog) KITGC AP00656 Ref, Ranatuerin- GIMDSVKNAAKNLAGQLLDTIKCK 2471 2PLe (frog) ITAC AP00657 Ref, Ranatuerin- GIMDTVKNAAKDLAGQLDKLKCR 2472 2PLf (frog) ITGC AP00658 Ref, Temporin- FLPLVGKILSGLI 2473 1PLa (frog) AP00659 Ref, Ranatuerin 5 FLPIASLLGKYL 2474 (frog) AP00661 Ref, Esculentin-2L GILSLFTGGIKALGKTLFKMAGKA 2475 (frog) GAEHLACKATNQC AP00662 Ref, Esculentin-2B GLFSILRGAAKFASKGLGKDLTKL 2476 (ESC2B-RANBE, GVDLVACKISKQC frog) AP00663 Ref, Esculentin-2P GFSSIFRGVAKFASKGLGKDLARL 2477 (frog) GVNLVACKISKQC AP00664 Ref, Peptide A1 FLPAIAGILSQLF 2478 (frog) AP00665 Ref, Peptide B9 FLPLIAGLIGKLF 2479 (frog) AP00666 Ref, PG-L ( frog) EGGGPQWAVGHFM 2480 AP00667 Ref, PG-KI (frog) EPHPDEFVGLM 2481 AP00668 Ref, PG-KII (frog) EPNPDEFVGLM 2482 AP00669 Ref, PG-KIII (frog) EPHPNEFVGLM 2483 AP00670 Ref, PG-SPI (frog) EPNPDEFFGLM 2484 AP00660 Ref, Pandinin 2 FWGALAKGALKLIPSLFSSFSKKD 2485 (African scorpion) AP00671 Ref, PG-SPII (frog) EPNPNEFFGLM 2486 AP00673 Ref, Lantibiotic WKSESVCTPGCVTGVLQTCFLQTI 2487 Ericin S (bacteria TCNCHISK AP00674 Ref, Lantibiotic VLSKSLCTPGCITGPLQTCYLCFPT 2488 Ericin_A (bacteria FAKC AP00675 Ref, Human beta FELDRICGYGTARCRKKCRSQEYRI 2489 defensin 4 (HBD-4, GRCPNTYACCLRKWDESLLNRTKP HBD4, human defensin) AP00676 Ref, RL-37 (RL37, RLGNFFRKVKEKIGGGLKKVGQKI 2490 monkey KDFLGNLVPRTAS cathelicidin) AP00677 Ref, CAP11 GLRKKFRKTRKRIQKLGRKIGKTG 2491 (Guinea pig RKVWKAWREYGQIPYPCRI cathelicidin) AP00678 Ref, Canine RLKELITTGGQKIGEKIRRIGQRIKD 2492 cathelicidin FFKNLQPREEKS (K9CATH)(dog) AP00679 Ref, Esculentin GLFSILKGVGKIAIKGLGKNLGKM 2493 2VEb (frog) GLDLVSCKISKEC AP00680 Ref, SMAP-34 GLFGRLRDSLQRGGQKILEKAERI 2494 (sheep cathelicidin) WCKIKDIFR AP00681 Ref, OaBac5 RFRPPIRRPPIRPPFRPPFRPPVRPPIR 2495 (sheep cathelicidin) PPFRPPFRPPIGPFP AP00682 Ref, OaBac6 RRLRPRHQHFPSERPWPKPLPLPLP 2496 (sheep cathelicidin) RPGPRPWPKPLPLPLPRPGLRPWPK PL AP00683 Ref, OaBac7.5 RRLRPRRPRLPRPRPRPRPRPRSLPL 2497 (sheep cathelicidin) PRPQPRRIPRPILLPWRPPRPIPRPQI QPIPRWL AP00684 Ref, OaBac11 RRLRPRRPRLPRPRPRPRPRPRSLPL 2498 (sheep cathelicidin) PRPKPRPIPRPLPLPRPRPKPIPRPLP LPRPRPRRIPRPLPLPRPRPRPIPRPL PLPQPQPSPIPRPL AP00685 Ref, Ranatuerin GIMDTVKGVAKTVAASLLDKLKC 2499 2VEb (frog) KITGC AP00686 Ref, eCATH-1 KRFGRLAKSFLRMRILLPRRKILLA 2500 (horse cathelicidin) S AP00687 Ref, eCATH-2 KRRHWFPLSFQEFLEQLRRFRDQL 2501 (horse cathelicidin) PFP AP00688 Ref, eCATH-3 KRFHSVGSLIQRHQQMIRDKSEAT 2502 (horse cathelicidin) RHGIRIITRPKLLLAS AP00689 Ref, Prophenin-1 AFPPPNVPGPRFPPPNFPGPRFPPPN 2503 (pig cathelicidin) FPGPRFPPPNFPGPRFPPPNFPGPPFP PPIFPGPWFPPPPPFRPPPFGPPRFP AP00690 Ref, Prophenin-2 AFPPPNVPGPRFPPPNVPGPRFPPPN 2504 (pig cathelicidin) FPGPRFPPPNFPGPRFPPPNFPGPPFP PPIFPGPWFPPPPPFRPPPFGPPRFP AP00691 Ref, HFIAP-1 GFFKKAWRKVKHAGRRVLDTAK 2505 (hagfish GVGRHYVNNWLNRYR cathelicidin) AP00692 Ref, HFIAP-3 GWFKKAWRKVKNAGRRVLKGVG 2506 (hagfish IHYGVGLI cathelicidin) AP00693 Ref, Trout cath RICSRDKNCVSRPGVGSIIGRPGGG 2507 (fish cathelicidin) SLIGRPGGGSVIGRPGGGSPPGGGS FNDEFIRDHSDGNRFA AP00694 Ref, MRP AIGSILGALAKGLPTLISWIKNR 2508 (melittin-related peptide) AP00695 Ref, Temporin- FLPILGKLLSGIL 2509 1TGa (frog) AP00696 Ref, Dahlein 1.1 GLFDIIKNIVSTL 2510 (frog) AP00697 Ref, Dahlein 1.2 GLFDIIKNIFSGL 2511 (frog) AP00698 Ref, Dahlein 4.1 GLWQLIKDKIKDAATGFVTGIQS 2512 (frog) AP00699 Ref, Dahlein 4.2 GLWQFIKDKLKDAATGLVTGIQS 2513 (frog) AP00700 Ref, Dahlein 4.3 GLWQFIKDKFKDAATGLVTGIQS 2514 (frog) AP00701 Ref, Dahlein 5.1 GLLGSIGNAIGAFIANKLKP 2515 (frog) AP00702 Ref, Dahlein 5.2 GLLGSIGNAIGAFIANKLKPK 2516 (frog) AP00703 Ref, Dahlein 5.3 GLLASLGKVLGGYLAEKLKP 2517 (frog) AP00704 Ref, Dahlein 5.4 GLLGSIGKVLGGYLAEKLKPK 2518 (frog) AP00705 Ref, Dahlein 5.5 GLLASLGKVLGGYLAEKLKPK 2519 (frog) AP00706 Ref, Dahlein 5.6 GLLASLGKVFGGYLAEKLKPK 2520 (frog) AP00709 Ref, Mytilus GFGCPNDYPCHRHCKSIPGRAGGY 2521 defensin (mytilin) CGGAHRLRCTCYR A (mollusc) AP00711 Ref, Mussel GFGCPNNYACHQHCKSIRGYCGG 2522 defensin MGD2 YCAGWFRLRCTCYRCG AP00712 Ref, scorpion GFGCPLNQGACHRHCRSIRRRGGY 2523 defensin CAGFFKQTCCYRN AP00713 Ref, Androctonus GFGCPFNQGACHRHCRSIRRRGGY 2524 defensin CAGLFKQTCTCYR AP00714 Ref, Orinthodoros GYGCPFNQYQCHSHCSGIRGYKGG 2525 defensin A (soft YCKGTFKQTCKCY ticks) AP00715 Ref, VaD1 (plant RTCMKKEGWGKCLIDTTCAHSCK 2526 defensin) NRGYIGGNCKGMTRTCYCLVNC AP00722 Ref, Cryptonin GLLNGLALRLGKRALKKIIKRLCR 2527 (insect, cicada) AP00723 Ref, Decoralin SLLSLLRKLIT 2528 (insect) AP00724 Ref, RTD-2 (rhesus RCLCRRGVCRCLCRRGVC 2529 theta-defensin-2, minidefensin, XXC, BBS, lectin, ZZHa) AP00725 Ref, RTD-3 (rhesus RCICTRGFCRCICTRGFC 2530 theta-defensin-3, minidefensin, XXC, BBS, lectin, ZZHa) AP00726 Ref, Combi-1 RRWWRF 2531 (synthetic) AP00748 Ref, Gm pro-rich DIQIPGIKKPTHRDIIIPNWNPNVRT 2532 pept1 (insect) QPWQRFGGNKS AP00749 Ref, Gm anionic EADEPLWLYKGDNIERAPTTADHP 2533 pept 1 (insect) ILPSIIDDVKLDPNRRYA AP00750 Ref, Gm pro-rich EIRLPEPFRFPSPTVPKPIDIDPILPHP 2534 pept 2 (insect) WSPRQTYPIIARRS AP00752 Ref, Gm defensin- DKLIGSCVWGATNYTSDCNAECK 2535 like peptide (insect) RRGYKGGHCGSFWNVNCWCEE AP00753 Ref, Gm VQETQKLAKTVGANLEETNKKLA 2536 apolipophoricin PQIKSAYDDFVKQAQEVQKKLHE (insect) AASKQ AP00754 Ref, Gm anionic ETESTPDYLKNIQQQLEEYTKNFNT 2537 pept2 (insect) QVQNAFDSDKIKSEVNNFIESLGKI LNTEKKEAPK AP00755 Ref, Gm cecropin ENFFKEIERAGQRIRDAIISAAPAVE 2538 D-like pept, insect TLAQAQKIIKGGD AP00756 Ref, Dermaseptin- ALWKDILKNAGKAALNEINQLVN 2539 B6 (DRS-B6, DRS Q B6, XXA, frog) AP00759 Ref, Phylloseptin- FLSLIPHAINAVSTLVHHSG 2540 O1 (PLS-O1, Phylloseptin-4, PS- 4, XXA, frog) AP00760 Ref, Phylloseptin- FLSLIPHAINAVSAIAKHS 2541 O2 (PLS-O2, Phylloseptin-5, PS- 5, XXA, frog) AP00761 Ref, Phylloseptin-6 SLIPHAINAVSAIAKHF 2542 (Phylloseptin-H4, PLS-H4, PS-6, XXA, frog) AP00762 Ref, Phylloseptin-7 FLSLIPHAINAVSAIAKHF 2543 (Phylloseptin-H5, PLS-H5, PS-7, XXA, frog) AP00763 Ref, Dermaseptin GLWSTIKNVGKEAAIAAGKAALG 2544 DPh-1 (XXA, frog) AL AP00764 Ref, Dermaseptin- GLRSKIWLWVLLMIWQESNKFKK 2545 S9 (DRS-S9, DRS M S9, frog) AP00765 Ref, Human salvic MHDFWVLWVLLEYIYNSACSVLS 2546 ATSSVSSRVLNRSLQVKVVKITN AP00766 Ref, Gassericin_A IYWIADQFGIHLATGTARKLLDAM 2547 (XXC, XXD2, ASGASLGTAFAAILGVTLPAWALA class IV AAGALGATAA bacteriocin, Gram- positive bacteria) AP00767 Ref, Circularin A VAGALGVQTAAATTIVNVILNAGT 2548 (XXC, class IV LVTVLGIIASIASGGAGTLMTIGWA bacteriocin, Gram- TFKATVQKLAKQSMARAIAY positive bacteria) AP00768 Ref, Closticin 574 PNWTKIGKCAGSIAWAIGSGLFGG 2549 (bacteria) AKLIKIKKYIAELGGLQKAAKLLV GATTWEEKLHAGGYALINLAAELT GVAGIQANCF AP00769 Ref, Caerin 1.11 GLLGAMFKVASKVLPHVVPAITEH 2550 (XXA, frog) F AP00770 Ref, Maculatin 1.4 GLLGLLGSVVSHVLPAITQHL 2551 (XXA, frog) AP00771 Ref, Magainin 1 GIGKFLHSAGKFGKAFVGEIMKS 2552 (frog) AP00772 Ref, Oxyopinin 1 FRGLAKLLKIGLKSFARVLKKVLP 2553 (spider) KAAKAGKALAKSMADENAIRQQN Q AP00773 Ref, Oxyopinin 2a GKFSVFGKILRSIAKVFKGVGKVR 2554 (spider) KQFKTASDLDKNQ AP00774 Ref, Oxyopinin 2b GKFSGFAKILKSIAKFFKGVGKVR 2555 (spider) KGFKEASDLDKNQ AP00775 Ref, Oxyopinin 2c GKLSGISKVLRAIAKFFKGVGKAR 2556 (spider) KQFKEASDLDKNQ AP00776 Ref, Oxyopinin 2d GKFSVFSKILRSIAKVFKGVGKVRK 2557 (spider) GFKTASDLDKNQ AP00777 Ref, NRC-1 (XXA, GKGRWLERIGKAGGIIIGGALDHL 2558 fish, gene predicted) AP00778 Ref, NRC-2 (XXA, WLRRIGKGVKIIGGAALDHL 2559 fish, gene predicted) AP00779 Ref, NRC-3 (XXA, GRRKRKWLRRIGKGVKIIGGAALD 2560 fish, gene HL predicted) AP00781 Ref, NRC-5 (XXA, FLGALIKGAIHGGRFIHGMIQNHH 2561 fish, gene predicted) AP00782 Ref, NRC-6 (XXA, GWGSIFKHGRHAAKHIGHAAVNH 2562 fish, gene YL predicted) AP00783 Ref, NRC-7 (XXA, RWGKWFKKATHVGKHVGKAALT 2563 fish, gene AYL predicted) AP00784 Ref, NRC-10 FFRLLFHGVHHVGKIKPRA 2564 (XXA, fish, gene predicted) AP00785 Ref, NRC-11 GWKSVFRKAKKVGKTVGGLALD 2565 (XXA, fish, gene HYL predicted) AP00786 Ref, NRC-12 GWKKWFNRAKKVGKTVGGLAVD 2566 (XXA, fish, gene HYL predicted) AP00787 Ref, NRC-13 GWRLLLKKAEVKTVGKLALKHYL 2567 (XXA, fish, gene predicted) AP00788 Ref, NRC-14 AGWGSIFKHIFKAGKFIHGAIQAHN 2568 (XXA, fish, gene D predicted) AP00789 Ref, NRC-15 GFWGKLFKLGLHGIGLLHLHL 2569 (XXA, fish, gene predicted) AP00790 Ref, NRC-16 GWKKWLRKGAKHLGQAAIK 2570 (XXA, fish, gene predicted) AP00791 Ref, NRC-17 GWKKWLRKGAKHLGQAAIKGLA 2571 (XXA, fish, gene S predicted) AP00792 Ref, NRC-19 FLGLLFHGVHHVGKWIHGLIHGHH 2572 (XXA, fish, gene predicted) AP00793 Ref, Bombinin H2 IIGPVLGLVGSALGGLLKKI 2573 (XXA, frog) AP00794 Ref, Bombinin H3 IIGPVLGMVGSALGGLLKKI 2574 (frog, XXD, XXA) AP00795 Ref, Bombinin H7 ILGPILGLVSNALGGLL 2575 (frog, XXD, XXA) AP00796 Ref, Bombinin GH- IIGPVLGLVGKPLESLLE 2576 1L (XXA, toad) AP00797 Ref, Bombinin GH- IIGPVLGLVGKPLESLLE 2577 1D (toad, XXD, XXA) AP00807 Ref, Enterocin E- NRWYCNSAAGGVGGAAGCVLAG 2578 760 (bacteriocin, YVGEAKENIAGEVRKGWGMAGGF bacteria) THNKACKSFPGSGWASG AP00808 Ref, hepcidin (fish) CRFCCRCCPRMRGCGLCCRF 2579 AP00809 Ref, hepcidin TH1- GIKCRFCCGCCTPGICGVCCRF 2580 5 (fish) AP00810 Ref, hepcidin TH2- QSHLSLCRWCCNCCRSNKGC 2581 3 (fish) AP00811 Ref, human LEAP- MTPFWRGVSLRPIGASCRDDSECIT 2582 2 RLCRKRRCSLSVAQE AP00812 Ref, Enkelytin FAEPLPSEEEGESYSKEPPEMEKRY 2583 (cow) GGFM AP00732 Ref, Spheniscin-1 SFGLCRLRRGSCAHGRCRFPSIPIG 2584 (Sphe-1, avian RCSRFVQCCRRVW defensin) AP00733 Ref, Organgutan LLGDFFRKAREKIGEEFKRIVQRIK 2585 ppyLL-37 (Great DFLRNLVPRTES Ape, primate cathelicidin) AP00734 Ref, Gibbon SLGNFFRKARKKIGEEFKRIVQRIK 2586 hmdSL-37 DFLQHLIPRTEA (hylobatidae, primate cathelicidin) AP00735 Ref, pobRL-37 RLGNFFRKAKKKIGRGLKKIGQKI 2587 (cercopithecidae, KDFLGNLVPRTES primate cathelicidin) AP00736 Ref, cjaRL-37 RLGDILQKAREKIEGGLKKLVQKI 2588 (primate KDFFGKFAPRTES cathelicidin) AP00737 Ref, Plasticin GLVTSLIKGAGKLLGGLFGSVTG 2589 PBN2KF (XXA, DRP-PBN2, frog) AP00738 Ref, Plasticin GLVTGLLKTAGKLLGDLFGSLTG 2590 ANCKF (XXA, synthetic) AP00739 Ref, Plasticin GVVTDLLKTAGKLLGNLFGSLSG 2591 PD36KF (XXA, synthetic) AP00740 Ref, Plasticin GVVTDLLKTAGKLLGNLVGSLSG 2592 PD36K (XXA, synthetic) AP00741 Ref, Chicken PITYLDAILAAVRLLNQRISGPCILR 2593 cathelicidin-B1 LREAQPRPGWVGTLQRRREVSFLV (bird cathelicidin)  EDGPCPPGVDCRSCEPGALQHCVG TVSIEQQPTAELRCRPLRPQ AP00742 Ref, Chicken MRILYLLLSVLFVVLQGVAGQPYF 2594 gallinacin 4 (Gal 4) SSPIHACRYQRGVCIPGPCRWPYY RVGSCGSGLKSCCVRNRWA AP00743 Ref, Chicken MKILCFFIVLFVAVHGAVGFSRSPR 2595 gallinacin 7 (Gal 7) YHMQCGYRGTFCTPGKCPYGNAY LGLCRPKYSCCRWL AP00744 Ref, Chicken MQILPLLFAVLLLMLRAEPGLSLA 2596 gallinacin 9 (Gal 9) RGLPQDCERRGGFCSHKSCPPGIGR IGLCSKEDFCCRSRWYS AP00745 Ref, Chicken MTPFWRGVSLRPVGASCRDNSECI 2597 LEAP-2 (cLEAP- TMLCRKNRCFLRTASE 2) AP00814 Ref, Caerulein GLGSILGKILNVAGKVGKTIGKVA 2598 precursor-related DAVGNKE fragment Ea (CPRF-Ea, frog) AP00815 Ref, Caerulein GLGSFLKNAIKIAGKVGSTIGKVAD 2599 precursor-related AIGNKE fragment Eb (CPRF-Eb, frog) AP00816 Ref, Caerulein GLGSFFKNAIKIAGKVGSTIGKVAD 2600 precursor-related AIGNKE fragment Ec (CPRF-Ec, frog) AP00817 Ref, Temporin-1Oa FLPLLASLFSRLL 2601 (frog) AP00818 Ref, Temporin-1Ob FLPLIGKILGTIL 2602 (frog) AP00819 Ref, Temporin-1Oc FLPLLASLFSRLF 2603 (frog) AP00820 Ref, Temporin-1Od FLPLLASLFSGLF 2604 (frog) AP00821 Ref, Brevinin-20a GLFNVFKGLKTAGKHVAGSLLNQ 2605 (frog) LKCKVSGGC AP00822 Ref, Brevinin-20b GIFNVFKGALKTAGKHVAGSLLNQ 2606 (frog) LKCKVSGEC AP00824 Ref, Temporin-1Gb SILPTIVSFLSKFL 2607 (XXA, frog) AP00825 Ref, Temporin-1Gc SILPTIVSFLTKFL 2608 (XXA, frog) AP00826 Ref, Temporin-1Gd FILPLIASFLSKFL 2609 (XXA, frog) AP00827 Ref, Ranatuerin- SMISVLKNLGKVGLGFVACKVNK 2610 1Ga (frog) QC AP00829 Ref, Ranalexin-1G FL GGLMKIIPAAFCAVTKKC 2611 (frog) AP00830 Ref, Ranatuerin-2G GLLLDTLKGAAKDIAGIALEKLKC 2612 (frog) KITGCKP AP00831 Ref, Odorranain- GLLSGILGAGKHIVCGLTGCAKA 2613 NR (frog) AP00832 Ref, Maximin H1 ILGPVISTIGGVLGGLLKNL 2614 (XXA, toad) AP00834 Ref, G. mellonella KVNANAIKKGGKAIGKGFKVISAA 2615 moricin-like STAHDVYEHIKNRRH peptide A (Gm- mlpA, insect) AP00835 Ref, G. mellonella GKIPVKAIKKGGQIIGKALRGINIAS 2616 moricin-like TAHDIISQFKPKKKKNH peptide B (Gm- mlpB, insect) AP00836 Ref, G. mellonella KVPIGAIKKGGKIIKKGLGVIGAAG 2617 moricin-like TAHEVYSHVKNRH peptide C1 (Gm- mlpC1 , insect) AP00837 Ref, G. mellonella KVPIGAIKKGGKIIKKGLGVLGAA 2618 moricin-like GTAHEVYNHVRNRQ peptide C2 (Gm- mlpC2, insect) AP00838 Ref, G. mellonella KVPIGAIKKGGKIIKKGLGVIGAAG 2619 moricin-like TAHEVYSHVKNRQ peptide C3 (Gm- mlpC3, insect) AP00839 Ref, G. mellonella KVPVGAIKKGGKAIKTGLGVVGA 2620 moricin-like AGTAHEVYSHIRNRH peptide C4/C5 (Gm-mlpC4/C5, insect) AP00840 Ref, G. mellonella KGIGSALKKGGKIIKGGLGALGAIG 2621 moricin-like TGQQVYEHVQNRQ peptide D (Gm- mlpD, insect) AP00841 Ref, Enterocin_A TTHSGKYYGNGVYCTKNKCTVD 2622 (EntA, class IIA WAKATTCIAGMSIGGFLGGAIPGK bacteriocin, i.e. C pediocin-like peptide, bacteria) AP00842 Ref, Divercin V41 TKYYGNGVYCNSKKCWVDWGQA 2623 (DvnV4l, class IIa SGCIGQTVVGGWLGGAIPGKC bacteriocin, pediocin-like peptide, bacteria. DvnRV41 is the recombinant form) AP00843 Ref, Divergicin TKYYGNGVYCNSKKCWVDWGTA 2624 M35 (class IIa QGCIDVVIGQLGGGIPGKGKC bacteriocin, pediocin-like peptide, bacteria) AP00844 Ref, Coagulin KYYGNGVTCGKHSCSVDWGKATT 2625 (bacteriocin, CIINNGAMAWATGGHQGTHKC pediocin-like peptide, bacteria) AP00845 Ref, Listeriocin KSYGNGVHCNKKKCWVDWGSAIS 2626 743A (class IIa TIGNNSAANWATGGAAGWKS bacteriocin, pediocin-like peptide, bacteria) AP00846 Ref, Mundticin KS KYYGNGVSCNKKGCSVDWGKAIG 2627 (enterocin CRL35, IIGNNSAANLATGGAAGWKS mundticin_ATO6, mundticin QU2, class IIa bacteriocin, pediocin-like peptide, bacteria) AP00847 Ref, Sakacin 5X KYYGNGLSCNKSGCSVDWSKAISII 2628 (Sak5X, class IIa GNNAVANLTTGGAAGWKS bacteriocin, pediocin-like peptide, bacteria) AP00848 Ref, Leucocin C KNYGNGVHCTKKGCSVDWGYAW 2629 (class IIa ANIANNSVMNGLTGGNAGWHN bacteriocin, pediocin-like peptide, bacteria) AP00849 Ref, Lactococcin TSYGNGVHCNKSKCWIDVSELETY 2630 MMFII (class IIa KAGTVSNPKDILW bacteriocin, pediocin-like peptide, bacteria) AP00850 Ref, Sakacin G KYYGNGVSCNSHGCSVNWGQAW 2631 (SakG, class IIa TCGVNHLANGGHGVC bacteriocin, pediocin-like peptide, bacteria) AP00851 Ref, Plantaricin KYYGNGVTCGKHSCSVNWGQAFS 2632 423 (class IIa CSVSHLANFGHGKC bacteriocin, pediocin-like peptide, bacteria) AP00852 Ref, Plantaricin KYYGNGLSCSKKGCTVNWGQAFS 2633 C19 (class IIa CGVNRVATAGHHKC bacteriocin, pediocin-like peptide, bacteria) AP00853 Ref, Enterocin P ATRSYGNGVYCNNSKCWVNWGE 2634 (EntP, class IIa AKENIAGIVISGWASGLAGMGH bacteriocin, pediocin-like peptide, bacteria) AP00854 Ref, Bacteriocin 31 ATYYGNGLYCNKQKCWVDWNKA 2635 (Bac 31, Bac31, SREIGKHVNGWVQHGPWAPR class IIa bacteriocin, pediocin-like peptide, bacteria) AP00855 Ref, MSI-78 GIGKFLKKAKKFGKAFVKILKK 2636 (XXA, synthetic) AP00856 Ref, MSI-594 GIGKFLKKAKKGIGAVLKVLTTGL 2637 (XXA, synthetic) AP00857 Ref, Catestatin SSMKLSFRARAYGFRGPGPQL 2638 (human CHGA(352-372), human Cst) AP00858 Ref, Temporin D LLPIVGNLLNSLL 2639 (XXA, frog) AP00859 Ref, Temporin H LSPNLLKSLL 2640 (XXA, frog) AP00861 Ref, Brevinin-ALb FLPLAVSLAANFLPKLFCKITKKC 2641 (frog) AP00862 Ref, Brevinin 1E FLPLLAGLAANFLPKIFCKITKRC 2642 (frog) AP00863 Ref, Temporin- FLPIVGKLLSGLSGLL 2643 ALa (XXA, frog) AP00864 Ref, Temporin FLPIVGRLISGLL 2644 1ARa (XXA, frog) AP00865 Ref, Temporin FLPIIGQLLSGLL 2645 1AUa (XXA, Temporin-AUa) (frog) AP00866 Ref, Temporin FLPIIAKVLSGLL 2646 1Bya (XXA, Temporin-1Bya, frog) AP00867 Ref, Temporin 1Ec FLPVIAGLLSKLF 2647 (XXA, frog) AP00869 Ref, Temporin 1Ja ILPLVGNLLNDLL 2648 (XXA, Temporin- 1Ja, frog) AP00873 Ref, Temporin 1Pra ILPILGNLLNGLL 2649 (XXA, frog) AP00874 Ref, Temporin 1VE FLPLVGKILSGLI 2650 (XXA, frog) AP00875 Ref, Temporin 1Va FLSSIGKILGNLL 2651 (XXA, frog) AP00876 Ref, Temporin 1Vb FLSIIAKVLGSLF 2652 (XXA, frog) AP00877 Ref, Brevinin-1Ja FLGSLIGAAIPAIKQLLGLKK 2653 (frog) AP00878 Ref, Brevinin- FLPILASLAAKFGPKLFCLVTKKC 2654 1BYa (frog) AP00884 Ref, Ixosin-B (tick) QLKVDLWGTRSGIQPEQHSSGKSD 2655 VRRWRSRY AP00885 Ref, Brevinin- FLPILASLAAKLGPKLFCLVTKKC 2656 1BYb (frog) AP00886 Ref, Brevinin- FLPILASLAATLGPKLLCLITKKC 2657 1BYc (frog) AP00887 Ref, Brevinin- GILSTFKGLAKGVAKDLAGNLLDK 2658 2BYa (frog) FKCKITGC AP00888 Ref, Brevinin- GIMDSVKGLAKNLAGKLLDSLKC 2659 2BYb (frog) KITGC AP00891 Ref, Pilosulin 3 IIGLVSKGTCVLVKTVCKKVLKQG 2660 (Myr b III)(ants) AP00892 Ref, Pilosulin 4 PDITKLNIKKLTKATCKVISKGASM 2661 (Myr b IV)(ants) CKVLFDKKKQE AP00893 Ref, Pilosulin 5 DVKGMKKAIKGILDCVIEKGYDKL 2662 (Myr b III)(ants) AAKLKKVIQQLWE AP00894 Ref, Ocellatin 4 GLLDFVTGVGKDIFAQLIKQI 2663 (XXA, frog) AP00895 Ref, OH-CATH KRFKKFFKKLKNSVKKRAKKFFK 2664 (snake cathelicidin, KPRVIGVSIPF reptile cathelicidin, or elapid cathelicidins) AP00896 Ref, BF-CATH KRFKKFFKKLKKSVKKRAKKFFK 2665 (snake cathelicidin) KPRVIGVSIPF AP00897 Ref, NA-CATH KRFKKFFKKLKNSVKKRAKKFFK 2666 (snake cathelicidin) KPKVIGVTFPF AP00898 Ref, Temporin-1Sa FLSGIVGMLGKLF 2667 (XXA, frog) AP00899 Ref, Temporin-1Sb FLPIVTNLLSGLL 2668 (XXA, frog) AP00900 Ref, Temporin-1Sc FLSHIAGFLSNLF 2669 (XXA, frog) AP00913 Ref, Ib-AMP1 EWGRRCCGWGPGRRYCVRWC 2670 (IbAMP1, plant defensin) AP00914 Ref, Ib-AMP2 QYGRRCCNWGPGRRYCKRWC 2671 (IBAMP2, plant defensin) AP00915 Ref, Ee-CBP QQCGRQAGNRRCANNLCCSQYGY 2672 (EeCBP, plant CGRTNEYCCTSQGCQSQCRRCG defensin, hevein- type, E. europaeus chitin-binding protein) AP00916 Ref, Pa-AMP1 AGCIKNGGRCNASAGPPYCCSSYC 2673 (PaAMP1, plant FQIAGQSYGVCKNR defensin, C6 type) AP00917 Ref, Pa-AMP2 ACIKNGGRCVASGGPPYCCSNYCL 2674 (PaAMP2, plant QIAGQSYGVCKKH defensin, C6 type) AP00924 Ref, Ornithodoros GYGCPFNQYQCHSHCRGIRGYKG 2675 defensin B (soft GYCTGRFKQTCKCY ticks) AP00925 Ref, Ornithodoros GYGCPFNQYQCHSHCSGIRGYKGG 2676 defensin C (soft YCKGLFKQTCNCY ticks) AP00926 Ref, Ornithodoros GFGCPFNQYECHAHCSGVPGYKG 2677 defensin D (soft GYCKGLFKQTCNCY ticks) AP00927 Ref, IYFIADKMGIQLAPAWYQDIVNWV 2678 Butyrivibriocin SAGGTLTTGFAIIVGVTVPAWIAEA AR10 (XXC, class AAAFGIASA IV bacteriocin, gram-positive bacteria) AP00929 Ref, AS-48 ASLQFLPIAHMAKEFGIPAAVAGT 2679 (enterocin 4, XXC, VINVVEAGGWVTTIVSILTAVGSG class IV bacteriocin GLSLLAAAGRESIKAYLKKEIKKK or class IId GKRAVIAW bacteriocin, Gram- positive bacteria) AP00930 Ref, Reutericin 6 IYWIADQFGIHLATGTARKLLDAM 2680 (XXC, XXD1, ASGASLGTAFAAILGVTLPAWALA class IV AAGALGATAA bacteriocin, Gram- positive bacteria) AP00931 Ref, Uberolysin LAGYTGIASGTAKKVVDAIDKGAA 2681 (XXC, class IV AFVIISIISTVISAGALGAVSASADFI bacteriocin, Gram- ILTVKNYISRNLKAQAVIW positive bacteria) AP00932 Ref, Acidocin_B IYWIADQFGIHLATGTARKLLDAV 2682 (XXC, class IV ASGASLGTAFAAILGVTLPAWALA bacteriocin, Gram- AAGALGATAA positive bacteria) AP00980 Ref, Phormia ATCDLLSGTGINHSACAAHCLLRG 2683 defensin B (insect NRGGYCNRKGVCVCRN defensin B) AP00990 Ref, Pth-St1 (plant RNCESLSHRFKGPCTRDSN 2684 defensin) AP00991 Ref, Snakin-1 GSNFCDSKCKLRCSKAGLADRCLK 2685 (StSN1, plant YCGICCEECKCVPSGTYGNKHECP defensin) CYRDKKNSKGKSKCP AP00992 Ref, Snakin-2 YSYKKIDCGGACAARCRLSSRPRL 2686 (StSN2, plant CNRACGTCCARCNCVPPGTSGNTE defensin) TCPCYASLTTHGNKRKCP AP00993 Ref, So-D2 (S. GIFSSRKCKTPSKTFKGICTRDSNC 2687 oleracea defensin DTSCRYEGYPAGDCKGIRRRCMCS D2, plant defensin) KPC AP00994 Ref, So-D6 (S. GIFSNMYARTPAGYFRGP 2688 oleracea defensin D6, plant defensin) AP00997 Ref, Nisin Q ITSISLCTPGCKTGVLMGCNLKTAT 2689 (lantibiotic, CNCSVHVSK bacteriocins, bacteria) AP01008 Ref, Tachystatin YSRCQLQGFNCVVRSYGLPTIPCC 2690 A1 (BBS, RGLTCRSYFPGSTYGRCQRF horseshoe crabs) AP01009 Ref, Tachystatin C DYDWSLRGPPKCATYGQKCRTWS 2691 (BBS, horseshoe PRNCCWNLRCKAFRCRPR crabs) AP01012 Ref, Latarcin 3a SWKSMAKKLKEYMEKLKQRA 2692 (Ltc3a, XXA, BBM, spider) AP01013 Ref, Latarcin 3b SWASMAKKLKEYMEKLKQRA 2693 (Ltc3b, XXA, BBM, spider) AP01014 Ref, Latarcin 4a GLKDKFKSMGEKLKQYIQTWKAK 2694 (Ltc4a, XXA, F BBM, spider) AP01015 Ref, Latarcin 4b SLKDKVKSMGEKLKQYIQTWKAK 2695 (Ltc4b, XXA, F BBM, spider) AP01016 Ref, Latarcin 5 GFFGKMKEYFKKFGASFKRRFANL 2696 (Ltc5, XXA, BBM, KKRL spider) AP01018 Ref, Latarcin 6a QAFQTFKPDWNKIRYDAMKMQTS 2697 (Ltc6a, BBM, LGQMKKRFNL spider) AP01019 Ref, Latarcin 7 GETFDKLKEKLKTFYQKLVEKAED 2698 (Ltc7, BBM, LKGDLKAKLS spider) AP01049 Ref, Kalata B2 VCGETCFGGTCNTPGCSCTWPICT 2699 (plant cyclotides, RDGLP XXC) AP01141 Ref, Cryptdin-6 LRDLVCYCRARGCKGRERMNGTC 2700 (Crp6, animal RKGHLLYMLCCR defensin, alpha, mouse) AP01142 Ref, Rabbit kidney KPYCSCKWRCGIGEEEKGICHKFPI 2701 defensin RK-2 VTYVCCRRP (animal defensin, alpha-defensin) AP01146 Ref, Gallinacin 6 DTLACRQSHGSCSFVACRAPSVDI 2702 (Gal6, Gal-6, avian GTCRGGKLKCCKWAPSS beta defensin, bird) AP01147 Ref, Gallinacin 8 DTVACRIQGNFCRAGACPPTFTISG 2703 (Gal8, Gal-8, avian  QCHGGLLNCCAKIPAQ beta defensin, bird) AP01148 Ref, Gallinacin 3 IATQCRIRGGFCRVGSCRFPHIAIGK 2704 (Gal3, Gal-3, avian CATFISCCGRAY beta defensin, bird) AP01152 Ref, Lactococcin Q SIWGDIGQGVGKAAYWVGKAMG 2705 (class IIb NMSDVNQASRINRKKKH bacteriocin, bacteria, chain a. For chain b, see Info) AP01155 Ref, Enterocin ESVFSKIGNAVGPAAYWILKGLGN 2706 1071 (Ent1071A, MSDVNQADRINRKKH class IIb bacteriocin, bacteria; chain B is Enterocin 1071B or Ent1071B, see info) AP01156 Ref, Plantaricin S NKLAYNMGHYAGKATIFGLAAW 2707 (chain a, class IIb ALLA bacteriocin, bacteria) AP01159 Ref, Hinnavin II KWKIFKKIEHMGQNIRDGLIKAGP 2708 (Hin II, XXA, AVQVVGQAATIYK insect) AP01160 Ref, NK-2 KILRGLCKKIMRSFLRRISWDILTG 2709 (synthetic, XXA) KK AP01167 Ref, Plantaricin LTTKLWSSWGYYLGKKARWNLK 2710 NC8 (PLNC8, HPYVQF chain a, class IIb bacteriocin, bacteria. For chain b, see Info) AP01168 Ref, Carnocyclin A LVAYGIAQGTAEKVVSLINAGLTV 2711 (a circular GSIISILGGVTVGLSGVFTAVKAAI bacteriocin, XXC, AKQGIKKAIQL bacteria) AP01169 Ref, Lactacin F NRWGDTVLSAASGAGTGIKACKSF 2712 (LafX, class IIb GPWGMAICGVGGAAIGGYFGYTH bacteriocin, N bacteria. For LafA, see Info) AP01170 Ref, Brochocin C YSSKDCLKDIGKGIGAGTVAGAAG 2713 (BrcC, chain BrcA, GGLAAGLGAIPGAFVGAHFGVIGG class IIb SAACIGGLLGN bacteriocin, bacteria. For BrcB, see Info) AP01171 Ref, Thermophilin YSGKDCLKDMGGYALAGAGSGAL 2714 13 (chain a ThmA, WGAPAGGVGALPGAFVGAHVGAI 2-chain class IIb AGGFACMGGMIGNKFN bacteriocin, bacteria. For chain B ThmB, see Info) AP01172 Ref, ABP-118 KRGPNCVGNFLGGLFAGAAAGVP 2715 (chain a: LGPAGIVGGANLGMVGGALTCL Abp118alpha, class IIb bacteriocin, bacteria. For chain b: Abp118beta, see Info) AP01173 Ref, Salivaricin P KRGPNCVGNFLGGLFAGAAAGVP 2716 (chain a: Sln1; LGPAGIVGGANLGMVGGALTCL class IIb bacteriocin, bacteria. For chain b: Sln2, see Info) AP01174 Ref, Mutacin IV KVSGGEAVAAIGICATASAAIGGL 2717 (chain a: NlmA, AGATLVTPYCVGTWGLIRSH class IIb bacteriocin, bacteria. For chain b: NLmB, see Info) AP01175 Ref, Lactocin 705 GMSGYIQGIPDFLKGYLHGISAAN 2718 (chain a: KHKKGRLGY Lac705alpha; class IIb bacteriocin, bacteria. For chain b: Lac705beta, see Info) AP01176 Ref, Cytolysin TTPACFTIGLGVGALFSAKFC 2719 (Cy1LS, bacteria; Chain B: Cy1LL) AP01177 Ref, Plantaricin EF FNRGGYNFGKSVRHVVDAIGSVA 2720 (chain a. PlnE, GILKSIR class IIb bacteriocin, bacteria. Chain b: PlnF) AP01178 Ref, Plantaricin JK GAWKNFWSSLRKGFYDGEAGRAI 2721 (chain a: PlnJ; class RR IIb bacteriocin, bacteria. Chain b: PlnK) AP01179 Ref, Enterocin SE- NGVYCNKQKCWVDWSRARSEIID 2722 K4 (class IIa RGVKAYVNGFTKVLGGIGGR bacteriocin, bacteria) AP01180 Ref, Acidocin NPKVAHCASQIGRSTAWGAVSGA 2723 J1132 (class IIb bacteriocin, bacteria) AP01181 Ref, Curvaticin AYPGNGVHCGKYSCTVDKQTAIG 2724 L442 (class IIa NIGNNAA bacteriocin, bacteria) AP01182 Ref, Bacteriocin 32 FTPSVSFSQNGGVVEAAAQRGYIY 2725 (Bac 32, class IIa KKYPKGAKVPNKVKMLVNIRGKQ bacteriocin, TMRTCYLMSWTASSRTAKYYYYI bacteria) AP01183 Ref, Bacteriocin 43 ATYYGNGLYCNKEKCWVDWNQA 2726 (Bac 43, KGEIGKIIVNGWVNHGPWAPRR bacteriocin, bacteria) AP01184 Ref, Bacteriocin T8 ATYYGNGLYCNKEKCWVDWNQA 2727 (Bac T8, class IIa KGEIGKIIVNGWVNHGPWAPRR bacteriocin, bacteria) AP01185 Ref, Enterocin_B ENDHRMPNNLNRPNNLSKGGAKC 2728 (EntB, bacteriocin, GAAIAGGLFGIPKGPLAWAAGLAN bacteria) VYSKCN AP01186 Ref, Acidocin_A KTYYGTNGVHCTKKSLWGKVRLK 2729 (bacteriocin, NVIPGTLCRKQSLPIKQDLKILLGW bacteria) ATGAFGKTFH AP01187 Ref, Enterocin Q MNFLKNGIAKWMTGAELQAYKK 2730 (EntQ, class IIc KYGCLPWEKISC bacteriocin, leaderless, i.e. no signal peptide, bacteria) AP01188 Ref, Enterocin MLAKIKAMIKKFPNPYTLAAKLTT 2731 EJ97 (EntEJ97, YEINWYKQQYGRYPWERPVA class IIc bacteriocin, leaderless, i.e. no signal peptide, bacteria) AP01189 Ref, Enterocin RJ- APAGLVAKFGRPIVKKYYKQIMQF 2732 11 (EntRJ-11, class IGEGSAINKIIPWIARMWRT IIc bacteriocin, leaderless, i.e. no signal sequence, bacteria) AP01190 Ref, Enterocin L50 MGAIAKLVAKFGWPIVKKYYKQI 2733 (old name: MQFIGEGWAINKIIEWIKKHI pediocin L50, EntL50A, a two- chain class IIc bacteriocin, leaderless, i.e. no signal peptide, bacteria. The sequence of EntL50B is provided in Info) AP01191 Ref, MR10 MGAIAKLVAKFGWPIVKKYYKQI 2734 (MR10A, class IIc MQFIGEGWAINKIIDWIKKHI bacteriocin, leaderless, i.e. no signal peptide, bacteria. For the sequence of chain b, see Info) AP01192 Ref, Halocin S8 SDCNINSNTAADVILCFNQVGSCA 2735 (HalS8, LCSPTLVGGPVP microhalocin, archaeocins, archeae) AP01193 Ref, Halocin C8 DIDITGCSACKYAAGQVCTIGCSA 2736 (HalC8, AGGFICGLLGITIPVAGLSCLGFVEI microhalocins, VCTVADEYSGCGDAVAKEACNRA archaeocins, GLC archaea) AP01194 Ref, Lacticin 3147 CSTNTFSLSDYWGNNGAWCTLTH 2737 (chain A1, a two- ECMAWCK chain lantibiotic, bacteriocin, bacteria. The sequence of chain A2 is given in Info; XXD3) AP01195 Ref, Salivaricin_A KRGSGWIATITDDCPNSVFVCC 2738 (SalA, lantibiotic, bacteriocin, bacteria) AP01196 Ref, Microcin E492 ATYYGNGLYCNKEKCWVDWNQA 2739 (MccE492, class KGEIGKIIVNGWVNHGPWAPRR IIb microcins, bacteriocin, bacteria; BBM; u- MccE492, siderophore peptide, BBI, XXG) AP01197 Ref, Hiracin JM79 ATYYGNGLYCNKEKCWVDWNQA 2740 (HirJM79, a Sec- KGEIGKIIVNGWVNHGPWAPRR dependent class II bacteriocin, bacteria) AP01198 Ref, Thermophilin LSCDEGMLAVGGLGAVGGPWGA 2741 9 (BlpDst, class IIb AVGVLVGAALYCF bacteriocin, bacteria. beta- chains: BlpUst, BlpEst, BapFst) AP01199 Ref, Penocin_A KYYGNGVHCGKKTCYVDWGQAT 2742 (PenA, class IIa ASIGKIIVNGWTQHGPWAHR bacteriocin, bacteria) AP01200 Ref, Salivaricin_B GGGVIQTISHECRMNSWQFLFTCC 2743 (SalB, lantibotic, S bacteriocin, bacteria) AP01201 Ref, Lacticin 481 KGGSGVIHTISHECNMNSWQFVFT 2744 (lantibiotic, class I  CCS bacteriocin, bacteria) AP01202 Ref, Bacteriocin KGGSGVIHTISHEVIYNSWNFVFTC 2745 J46 (BacJ46, CS bacteriocin, bacteria) AP01203 Ref, Nukacin_A KKKSGVIPTVSHDCHMNSFQFVFT 2746 (NucA, Nukacin CCS ISK-1, NukISK-1, bacteriocin, bacteria) AP01204 Ref, Streptococcin GKNGVFKTISHECHLNTWAFLATC 2747 A-FF22 CS (LANTIBIOTIC, class I bacteriocin, bacteria) AP01210 Ref, Jelleine-I PFKLSLHL 2748 (honeybees, insect, XXA) AP01211 Ref, Jelleine-II TPFKLSLHL 2749 (honeybees, insect, XXA) AP01212 Ref, Jelleine-III EPFKLSLHL 2750 (honeybees, insect, XXA) AP01213 Ref, EFRGSIVIQGTKEGKSRPSLDIDYK 2751 Hymenoptaecin QRVYDKNGMTGDAYGGLNIRPGQ (honeybees, insect PSRQHAGFEFGKEYKNGFIKGQSE defensin, XXcooh) VQRGPGGRLSPYFGINGGFRF AP01216 Ref, Ascaphin-1 GFRDVLKGAAKAFVKTVAGHIAN 2752 (frog, XXA) AP01218 Ref, Ascaphin-3 GFRDVLKGAAKAFVKTVAGHIANI 2753 (frog) AP01220 Ref, Ascaphin-5 GIKDWIKGAAKKLIKTVASNIANQ 2754 (frog) AP01222 Ref, Ascaphin-7 GFKDWIKGAAKKLIKTVASSIANQ 2755 (frog) AP01223 Ref, Ascaphin-8 GFKDLLKGAAKALVKTVLF 2756 (frog, XXA) AP01226 Ref, Microcin C7 MRTGNAD 2757 (MccC7, microcin C51, MccC51, class I microcins, bacteriocins, bacteria. Others: MccA; XXamp; BBPe) AP01227 Ref, Microcin_B17 VGIGGGGGGGGGGSCGGQGGGCG 2758 (MccB17, class I GCSNGCSGGNGGSGGSGSHI microcins, bacteriocins, Gram- negative bacteria; BBPe) AP01228 Ref, Microcin V ASGRDIAMAIGTLSGQFVAGGIGA 2759 (MccV, (old name) AAGGVAGGAIYDYASTHKPNPAM Colicin V, ColV; SPSGLGGTIKQKPEGIPSEAWNYAA class II microcins, GRLCNWSPNNLSDVCL bacteriocins, Gram- negative bacteria) AP01229 Ref, Microcin L GDVNWVDVGKTVATNGAGVIGG 2760 (MccL, class IIa AFGAGLCGPVCAGAFAVGSSAAV microcins, AALYDAAGNSNSAKQKPEGLPPEA bacteriocins, Gram- WNYAEGRMCNWSPNNLSDVCL negative bacteria) AP01230 Ref, Microcin M DGNDGQAELIAIGSLAGTFISPGFG 2761 (MccM, class IIb SIAGAYIGDKVHSWATTATVSPSM microcins, SPSGIGLSSQFGSGRGTSSASSSAGS bacteriocins, Gram- GS negative bacteria) AP01231 Ref, Microcin H47 GGAPATSANAAGAAAIVGALAGIP 2762 (MccH47, class IIb GGPLGVVVGAVSAGLTTGIGSTVG microcins, SGSASSSAGGGS bacteriocins, Gram- negative bacteria) AP01232 Ref, Microcin I47 MNLNGLPASTNVIDLRGKDMGTYI 2763 (MccI47, class IIb DANGACWAPDTPSIIMYPGGSGPS microcins, YSMSSSTSSANSGS bacteriocins, Gram- negative bacteria) Aibellin *Ac U A U A U A Q U F U G U U P V U U E E 2764 [NHC(CH2Ph)HCH2NHCH2CH2]OH Alamethicin_F-30 * Ac U P U A U A Q U V U G L U P V U U E Q F 2765 OH Alamethicin_F-50 * Ac U P U A U A Q U V U G L U P V U U Q Q F 2766 OH Alamethicin_II * Ac U P U A U U Q U V U G L U P V U U E Q F 2767 OH Ampullosporin * Ac W A U U L U Q U U U Q L U Q L OH 2768 Ampullosporin_B * Ac W A U U L U Q A U U Q L U Q L OH 2769 Ampullosporin_C * Ac W A U U L U Q U A U Q L U Q L OH 2770 Ampullosporin_D * Ac W A U U L U Q U U A Q L U Q L OH 2771 Ampullosporin_E1 * Ac W A U U L U Q A U U Q L A Q L OH 2772 Ampullosporin_E2 * Ac W A U U L U Q U A A Q L U Q L OH 2773 Ampullosporin_E3 * Ac W A U U L U Q U U A Q L A Q L OH 2774 Ampullosporin_E4 * Ac W A U U L U Q A A U Q L U Q L OH 2775 Antiamoebin_I * Ac F U U U J G L U U O Q J O U P F OH 2776 Antiamoebin_II * Ac F U U U J G L U U O Q J P U P F OH 2777 Antiamoebin_III * Ac F U U U U G L U U O Q J O U P F OH 2778 Antiamoebin_IV * Ac F U U U J G L U U O Q J O U P F OH 2779 Antiamoebin_V * Ac F U U U J A L U U O Q J O U P F OH 2780 Antiamoebin_VI * Ac F U U U U G L U U O Q U O U P F OH 2781 Antiamoebin_VII * Ac F A U J U G L U U O Q J O U P F OH 2782 Antiamoebin_VIII * Ac F U U U J G L U U O Q U O U P F OH 2783 Antiamoebin_IX * Ac F U A U J G L U U O Q J O U P F OH 2784 Antiamoebin_X * Ac F U U U J G L J U O Q U O U P F OH 2785 Antiamoebin_XI * Ac F U U U U A L U U O Q J O U P F OH 2786 Antiamoebin_XII * Ac F U U U U G L A U O Q J O U P F OH 2787 Antiamoebin_XIII * Ac V U U U U G L U U O Q J O U P F OH 2788 Antiamoebin_XIV * Ac V U U U V G L U U O Q J O U P F OH 2789 Antiamoebin_XV * Ac L U U U U G L U U O Q J O U P F OH 2790 Antiamoebin_XVI * Ac L U U U J G L U U O Q J O U P F OH 2791 Atroviridin_A * Ac U P U A U A Q U V U G L U P V U U Q Q F 2792 OH Atroviridin_B * Ac U P U A U A Q U V U G L U P V U J Q Q F 2793 OH Atroviridin_C * Ac U P U A U U Q U V U G L U P V U J Q Q F 2794 OH Bergofungin_A * Ac V U U U V G L U U O Q J O U F OH 2795 Bergofungin_B * Ac V U U U V G L V U O Q U O U F OH 2796 Bergofungin_C * Ac V U U U V G L U U O Q U O U F OH 2797 Bergofungin_D * Ac V U U V G L U U O Q U O U F OH 2798 Boletusin * Ac F U A U J L Q G U U A A U P U U U Q W 2799 OH Cephaibol_A * Ac F U U U U G L J U O Q J O U P F OH 2800 Cephaibol_A2 * Ac F U U U U A L J U O Q J O U P F OH 2801 Cephaibol_B * Ac F U U U J G L J U O Q J O U P F OH 2802 Cephaibol_C * Ac F U U U U G L J U O Q U O U P F OH 2803 Cephaibol_D * Ac F U U U U G L U U O Q U O U P F OH 2804 Cephaibol_E * Ac F U U U U G L U U O Q J O U P F OH 2805 Cephaibol_P * Ac F J Q U I T U L U O Q U O U P F S OH 2806 Cephaibol_Q * Ac F J Q U I T U L U P Q U O U P F S OH 2807 Cervinin_1 * Ac L U P U L U P A U P V L OH 2808 Cervinin_2 * Ac L U P U L U P A U P V L OCOCH3 2809 Chrysospermin_A * Ac F U S U U L Q G U U A A U P U U U Q W 2810 OH Chrysospermin_B * Ac F U S U U L Q G U U A A U P J U U Q W 2811 OH Chrysospermin_C * Ac F U S U J L Q G U U A A U P U U U Q W 2812 OH Chrysospermin_D * Ac F U S U J L Q G U U A A U P J U U Q W 2813 OH Clonostachin * Ac U O L J O L J O U J U O J I 2814 O[CH(CH(OH)CH2OH)CH(OH)CH(OH)CH2]OH Emerimicin_II_A * Ac W I Q U I T U L U O Q U O U P F OH 2815 Emerimicin_II_B * Ac W I Q J I T U L U O Q U O U P F OH 2816 Emerimicin_III * Ac F U U U V G L U U O Q J O U F OH 2817 Emerimicin_IV * Ac F U U U V G L U U O Q J  O A F OH 2818 Harzianin_HBI * Ac U N L I U P J L U P L OH 2819 Harzianin_HCI * Ac U N L U P S V U P U L U P L OH 2820 Harzianin_HC_III * Ac U N L U P S V U P J L U P L OH 2821 Harzianin_HC_IX * Ac U N L U P A I U P J L U P L OH 2822 Harzianin_HC_VI * Ac U N L U P A V U P U L U P L OH 2823 Harzianin_HC_VIII * Ac U N L U P A V U P J L U P L OH 2824 Harzianin_HC_VIII * Ac U N L U P A V U P J L U P L OH 2825 Harzianin_HC_X * Ac U Q L U P A V U P J L U P L OH 2826 Harzianin_HC_XI * Ac U N L U P S I U P U L U P L OH 2827 Harzianin_HC_XII * Ac U N L U P S I U P J L U P L OH 2828 Harzianin_HC_XIII * Ac U Q L U P S I U P J L U P L OH 2829 Harzianin_HC_XIV * Ac U N L U P A I U P U L U P L OH 2830 Harzianin_HC_XV * Ac U Q L U P A I U P J L U P L OH 2831 Harzianin_HK_VI * Ac U N I I U P L L U P L OH 2832 Harzianin_PCU4 * Ac U N L U P S I U P U L U P V OH 2833 Helioferin_A * Fa P ZZ A U I I U U AAE 2834 Helioferin_B * Fa P ZZ A U I I U U AMAE 2835 Heptaibin * Ac F U U U V G L U U O Q U O U F OH 2836 Hypelcin_A * Ac U P U A U U Q L U G U U U P V U U Q Q L 2837 OH Hypelcin_A_I * Ac U P U A U U Q U L U G U U P V U U Q Q L 2838 OH Hypelcin_A_II * Ac U P U A U A Q U L U G U U P V U U Q Q L 2839 OH Hypelcin_A_III * Ac U P U A U U Q U L U G U U P V U U Q Q 2840 [C7H16NO] Hypelcin_A_IV * Ac U P U A U U Q U I U G U U P V U U Q Q L 2841 OH Hypelcin_A-III * Ac U P U A U U Q U L U G U U P V U J Q Q L 2842 OH Hypelcin_A-IX * Ac U P U A U U Q U I U G U U P V U J Q Q L 2843 OH Hypelcin_A-V * Ac U P U A U U Q U L U G U U P V U U Q Q I 2844 OH Hypelcin_A-VI * Ac U P U A U A Q U L U G U U P V U U Q Q I 2845 OH Hypelcin_A-VII * Ac U P U A U A Q U L U G U U P V U J Q Q L 2846 OH Hypelcin_A-VIII * Ac U P U A U A Q U I U G U U P V U U Q Q L 2847 OH Hypelcin_B_I * Ac U P U A U U Q U L U G U U P V U U E Q L 2848 OH Hypelcin_B_II * Ac U P U A U A Q U L U G U U P V U U E Q L 2849 OH Hypelcin_B_III * Ac U P U A U U Q U L U G U U P V U J E Q L 2850 OH Hypelcin_B_IV * Ac U P U A U U Q U I U G U U P V U U E Q L 2851 OH Hypelcin_B_V * Ac U P U A U U Q U L U G U U P V U U E Q I 2852 OH Hypomurocin_A_I * Ac U Q V V U P L L U P L OH 2853 Hypomurocin_A_II * Ac J Q V V U P L L U P L OH 2854 Hypomurocin_A_III * Ac U Q V L U P L I U P L OH 2855 Hypomurocin_A_IV * Ac U Q I V U P L L U P L OH 2856 Hypomurocin_A_V * Ac U Q I I U P L L U P L OH 2857 Hypomurocin_A_Va * Ac U Q I L U P L I U P L OH 2858 Hypomurocin_B_I * Ac U S A L U Q U V U G U U P L U U Q V OH 2859 Hypomurocin_B_II * Ac U S A L U Q U V U G U U P L U U Q L OH 2860 Hypomurocin_B_IIIa * Ac U A A L U Q U V U G U U P L U U Q V OH 2861 Hypomurocin_B_IIIb * Ac U S A L U Q J V U G U U P L U U Q V OH 2862 Hypomurocin_B_IV * Ac U S A L U Q U V U G J U P L U U Q V OH 2863 Hypomurocin_B_V * Ac U S A L U Q U V U G J U P L U U Q L OH 2864 Leu1_Zervamicin * Ac L I Q J I T U L U O Q U O U P F OH 2865 Longibrachin_A_I * Ac U A U A U A Q U V U G L U P V U U Q Q F 2866 OH Longibrachin_A_II * Ac U A U A U A Q U V U G L U P V U J Q Q F 2867 OH Longibrachin_A_III * Ac U A U A U U Q U V U G L U P V U U Q Q F 2868 OH Longibrachin_A_IV * Ac U A U A U U Q U V U G L U P V U J Q Q F 2869 OH Longibrachin_B_II * Ac U A U A U A Q U V U G L U P V U U E Q F 2870 OH Longibrachin_B_III * Ac U A U A U A Q U V U G L U P V U J E Q F 2871 OH LP237_F5 * Oc U P Y U Q Q U Zor Q A L OH 2872 LP237_F7 * Ac U P F U Q Q U U Q A L OH 2873 LP237_F8 * Oc U P F U Q Q U Zor Q A L OH 2874 NA_VII * Ac U A A U J Q U U U S L U OCH3 2875 Paracelsin_A * Ac U A U A U A Q U V U G U U P V U U Q Q 2876 F OH Paracelsin_B * Ac U A U A U A Q U L U G U U P V U U Q Q F 2877 OH Paracelsin_C * Ac U A U A U U Q U V U G U U P V U U Q Q 2878 F OH Paracelsin_D * Ac U A U A U U Q U L U G U U P V U U Q Q F 2879 OH Paracelsin_E * Ac U A U A U A Q U L U G U A P V U U Q Q F 2880 OH Peptaibolin * Ac L U L U F OH 2881 Peptaivirin_A * Ac F U A U J L Q G U U A A U P J U U Q W 2882 OH Peptaivirin_B * Ac F U S U J L Q G U U A A U P J U U Q F OH 2883 Polysporin_A * Ac U P U A U U Q U V U G V U P V U U Q Q F 2884 OH Polysporin_B * Ac U P U A U U Q U V U G L U P V U U Q Q F 2885 OH Polysporin_C * Ac U P U A U U Q U I U G L U P V U U Q Q F 2886 OH Polysporin_D * Ac U P U A U U Q U I U G L U P V U V Q Q F 2887 OH Pseudokinin_KLIII * Ac U N I I U P L L U P NH2 2888 Pseudokinin_KLVI * Ac U N I I U P L V hydroxyketopiperazine 2889 Samarosporin_I * Ac F U U U V G L U U O Q J O A F OH 2890 Samarosporin_II * Ac F U U U V G L U U O Q J O U F OH 2891 Saturnisporin_SA_I * Ac U A U A U A Q U L U G U U P V U U Q Q F 2892 OH Saturnisporin_SA_II * Ac U A U A U A Q U L U G U U P V U J Q Q F 2893 OH Saturnisporin_SA_III * Ac U A U A U U Q U L U G U U P V U U Q Q F 2894 OH Saturnisporin_SA_IV * Ac U A U A U U Q U L U G U U P V U J Q Q F 2895 OH Stilbellin_I * Ac F U U U V G L U U O Q J O A F OH 2896 Stilbellin_II * Ac F U U U V G L U U O Q J O U F OH 2897 Stilboflavin_A_1 * Ac U P U A U A Q U V U G U U P V U U E Q V 2898 OH Stilboflavin_A_2 * Ac U P U A U A Q U L U G U U P V U U E Q V 2899 OH Stilboflavin_A_3 * Ac U P U A U U Q U V U G U A P V U U E Q L 2900 OH Stilboflavin_A_4 * Ac U P U A U A Q U L U G U U P V U U E Q L 2901 OH Stilboflavin_A_5 * Ac U P U A U U Q U L U G U U P V U U E Q V 2902 OH Stilboflavin_A_6 * Ac U P U A U A Q U L U G U U P V U U E Q J 2903 OH Stilboflavin_A_7 * Ac U P U A U U Q U L U G U U P V U U E Q I 2904 OH Stilboflavin_B_1 * Ac U P U A U A Q U V U G U U P V U U Q Q 2905 V OH Stilboflavin_B_2 * Ac U P U A U A Q U L U G U U P V U U Q Q V 2906 OH Stilboflavin_B_3 * Ac U P U A U A Q U V U G U U P V U U Q Q L 2907 OH Stilboflavin_B_4 * Ac U P U A U A Q U L U G U U P V U U Q Q L 2908 OH Stilboflavin_B_5 * Ac U P U A U U Q U L U G U U P V U U Q Q V 2909 OH Stilboflavin_B_6 * Ac U P U A U U Q U V U G U U P V U U Q Q 2910 V OH Stilboflavin_B_7 * Ac U P U A U U Q U L U G U U P V U U Q Q L 2911 OH Stilboflavin_B_8 * Ac U P U A U U Q U V U G U U P V U U Q Q L 2912 OH Stilboflavin_B_9 * Ac U P U A U U Q U L U G U U P V U U Q Q I 2913 OH Stilboflavin_B_10 * Ac U P U A U U Q U V U G U U P V U U Q Q I 2914 OH Suzukacillin * Ac U A U A U A Q U U U G L U P V U U Q Q F 2915 OH Trichobrachin_A-I * Ac U N L L U P L U U P L OH 2916 Trichobrachin_A-II * Ac U N L L U P V L U P V OH 2917 Trichobrachin_A-III * Ac U N V L U P L L U P V OH 2918 Trichobrachin_A-IV * Ac U N L V U P L L U P V OH 2919 Trichobrachin_B-I * Ac U N L L U P V U V P L OH 2920 Trichobrachin_B-II * Ac U N V L U P L U V P L OH 2921 Trichobrachin_B-III * Ac U N L V U P L U V P L OH 2922 Trichobrachin_B-IV * Ac U N L L U P L U V P V OH 2923 Trichocellin_TC-A-I * Ac U A U A U A Q U L U G U U P V U U Q Q F 2924 OH Trichocellin_TC-A-II * Ac U A U A U A Q U L U G U U P V U J Q Q F 2925 OH Trichocellin_TC-A-III * Ac U A U A U A Q U I U G U U P V U U Q Q F 2926 OH Trichocellin_TC-A-IV * Ac U A U A U A Q U I U G U U P V U J Q Q F 2927 OH Trichocellin_TC-A-V * Ac U A U A U A Q U L U G L U P V U U Q Q F 2928 OH Trichocellin_TC-A-VI * Ac U A U A U A Q U L U G L U P V U J Q Q F 2929 OH Trichocellin_TC-A- * Ac U A U A U A Q U I U G L U P V U U Q Q F 2930 VII OH Trichocellin_TC-A- * Ac U A U A U A Q U I U G L U P V U J Q Q F 2931 VIII OH Trichocellin_TC-B-I * Ac U A U A U A Q U L U G U U P V U U E Q F 2932 OH Trichocellin_TC-B-II * Ac U A U A U A Q U L U G U U P V U J E Q F 2933 OH Trichodecenin_TD_I * (Z)-4-decenoyl G G L U G I L OH 2934 Trichodecenin_TD_II * (Z)-4-decenoyl G G L U G L L OH 2935 Trichogin_A_IV * Oc U G L U G G L U G I L OH 2936 Trichokindin_Ia * Ac U S A U U Q J L U A U U P L U U Q I OH 2937 Trichokindin_Ib * Ac U S A U J Q U L U A U U P L U U Q I OH 2938 Trichokindin_IIa * Ac U S A U U Q U L U A J U P L U U Q I OH 2939 Trichokindin_IIb * Ac U S A U J Q J L U A U U P L U U Q L OH 2940 Trichokindin_IIIa * Ac U S A U U Q J L U A J U P L U U Q L OH 2941 Trichokindin_IIIb * Ac U S A U J Q U L U A J U P L U U Q L OH 2942 Trichokindin_IV * Ac U S A U J Q J L U A U U P L U U Q I OH 2943 Trichokindin_Va * Ac U S A U U Q J L U A J U P L U U Q I OH 2944 Trichokindin_Vb * Ac U S A U J Q U L U A J U P L U U Q I OH 2945 Trichokindin_VI * Ac U S A U J Q J L U A J U P L U U Q L OH 2946 Trichokindin_VII * Ac U S A U J Q J L U A J U P L U U Q I OH 2947 Trichokonin_Ia * Ac U A U A U A Q U V U G L A P V U U Q Q F 2948 OH Trichokonin_Ib * Ac U G U A U A Q U V U G L U P V U U Q Q F 2949 OH Trichokonin_IIa * Ac U A U A U A Q U V U G L U P A U U Q Q F 2950 OH Trichokonin_IIb * Ac A A U A U A Q U V U G L U P V U U Q Q F 2951 OH Trichokonin_IIc * Ac U A A A U A Q U V U G L U P V U U Q Q F 2952 OH Trichokonin_V * Ac U A U A U Q U V U G L U P V U U Q Q F 2953 OH Trichokonin_VII * Ac U A U A U A Q U V U G L U P V U J Q Q F 2954 OH Trichokonin_VIII * Ac U A U A U U Q U V U G L U P V U U Q Q F 2955 OH Trichokonin_IX * Ac U A U A U A Q U V U G L U P V U J Q Q F 2956 OH Tricholongin_BI * Ac U G F U U Q U U U S L U P V U U Q Q L 2957 OH Tricholongin_BII * Ac U G F U U Q U U U S L U P V U J Q Q L 2958 OH Trichopolyn_I * Fa P ZZ A U U I A U U AMAE 2959 Trichopolyn_II * Fa P ZZ A U U V A U U AMAE 2960 Trichopolyn_III * Fa P ZZ A U U I A U A AMAE 2961 Trichopolyn_IV * Fa P ZZ A U U V A U A AMAE 2962 Trichopolyn_V * Fa′P ZZ A U U I A U U AMAE 2963 Trichorovin_TV_Ia * Ac U N V Lx U P Lx Lx U P V OH 2964 Trichorovin_TV_Ib * Ac U N V V U P Lx Lx U P Lx OH 2965 Trichorovin_TV_IIa * Ac U N V V U P Lx Lx U P Lx OH 2966 Trichorovin_TV_IIb * Ac U N Lx V U P Lx Lx U P V OH 2967 Trichorovin_TV_IIIa * Ac U Q V V U P Lx Lx U P Lx OH 2968 Trichorovin_TV_IIIb * Ac U Q V Lx U P Lx Lx U P V OH 2969 Trichorovin_TV_IVa * Ac U Q V V U P Lx Lx U P Lx OH 2970 Trichorovin_TV_IVb * Ac U Q Lx V U P Lx Lx U P V OH 2971 Trichorovin_TV_IVc * Ac U N V Lx U P Lx Lx U P Lx OH 2972 Trichorovin_TV_IXa * Ac U Q V Lx U P Lx Lx U P Lx OH 2973 Trichorovin_TV_IXb * Ac U Q Lx Lx U P Lx Lx U P V OH 2974 Trichorovin_TV_Va * Ac U N V Lx U P Lx Lx U P Lx OH 2975 Trichorovin_TV_Vb * Ac U N Lx Lx U P Lx Lx U P V OH 2976 Trichorovin_TV_VIa * Ac U N V Lx U P Lx Lx U P Lx OH 2977 Trichorovin_TV_VIb * Ac U N Lx Lx U P Lx Lx U P V OH 2978 Trichorovin_TV_VIIa * Ac U N Lx V U P Lx Lx U P Lx OH 2979 Trichorovin_TV_VIIb * Ac U Q V Lx U P Lx Lx U P V OH 2980 Trichorovin_TV_VIII * Ac U Q V Lx U P Lx Lx U P Lx OH 2981 Trichorovin_TV_Xa * Ac U Q Lx V U P Lx Lx U P Lx OH 2982 Trichorovin_TV_Xb * Ac U N Lx Lx U P Lx Lx U P Lx OH 2983 Trichorovin_TV_XIIa * Ac U N I I U P L L U P I OH 2984 Trichorovin_TV_XIIb * Ac U N Lx Lx U P Lx Lx U P L OH 2985 Trichorovin_TV_XIII * Ac U Q Lx Lx U P Lx Lx U P Lx OH 2986 Trichorovin_TV_XIV * Ac U Q Lx Lx U P Lx Lx U P Lx OH 2987 Trichorozin_I * Ac U N I L U P I L U P V OH 2988 Trichorozin_II * Ac U Q I L U P I L U P V OH 2989 Trichorozin_III * Ac U N I L U P I L U P L OH 2990 Trichorozin_IV * Ac U Q I L U P I L U P L OH 2991 Trichorzianine_TA_IIIc * Ac U A A U U Q U U U S L U P V U I Q Q W 2992 OH Trichorzianine_TB_IIa * Ac U A A U U Q U U U S L U P L U I Q E W 2993 OH Trichorzianine_TB_IIIc * Ac U A A U U Q U U U S L U P V U I Q E W 2994 OH Trichorzianine_TB_IVb * Ac U A A U J Q U U U S L U P V U I Q E W 2995 OH Trichorzianine_TB_Vb * Ac U A A U U Q U U U S L U P L U I Q E F OH 2996 Trichorzianine_TB_VIa * Ac U A A U J Q U U U S L U P L U I Q E F OH 2997 Trichorzianine_TB_VIb * Ac U A A U U Q U U U S L U P V U I Q E F 2998 OH Trichorzianine_TB_VII * Ac U A A U J Q U U U S L U P V U I Q E F OH 2999 Trichorzin_HA_I * Ac U G A U U Q U V U G L U P L U U Q L OH 3000 Trichorzin_HA_II * Ac U G A U U Q U V U G L U P L U J Q L OH 3001 Trichorzin_HA_III * Ac U G A U J Q U V U G L U P L U U Q L OH 3002 Trichorzin_HA_V * Ac U G A U J Q U V U G L U P L U J Q L OH 3003 Trichorzin_HA_VI * Ac U G A U J Q J V U G L U P L U J Q L OH 3004 Trichorzin_HA_VII * Ac U G A U J Q V V U G L U P L U J Q L OH 3005 Trichorzin_MA_I * Ac U S A U U Q U L U G L U P L U U Q V OH 3006 Trichorzin_MA_II * Ac U S A U J Q U L U G L U P L U U Q V OH 3007 Trichorzin_MA_III * Ac U S A U J Q J L U G L U P L U U Q V OH 3008 Trichorzin_PA_II * Ac U S A U J Q U V U G L U P L U U Q W OH 3009 Trichorzin_PA_IV * Ac U S A U J Q J V U G L U P L U U Q W OH 3010 Trichorzin_PA_V * Ac U S A J J Q U V U G L U P L U U Q W OH 3011 Trichorzin_PA_VI * Ac U S A U J Q U V U G L U P L U U Q F OH 3012 Trichorzin_PA_VII * Ac U S A J J Q U V U G L U P L U U Q W OH 3013 Trichorzin_PA_VIII * Ac U S A U J Q J V U G L U P L U U Q F OH 3014 Trichorzin_PA_IX * Ac U S A J J Q U V U G L U P L U U Q F OH 3015 Trichorzin_PAU4 * Ac U S A U U Q U V U G L U P L U U Q  W OH 3016 Trichosporin_TS-B- * Ac U A G U A U Q U Lx A A Vx A P V U Vx Q 3017 1a-1 Q F OH Trichosporin_TS-B- * Ac U A G A U U Q U Lx A A Vx A P V U Vx Q 3018 1a-2 Q F OH Trichosporin_TS-B- * Ac U A G A U U Q U Lx U G Lx A P V U A Q 3019 1b Q F OH Trichosporin_TS-B- * Ac U A S A U U Q U Lx U G Lx A P V U U Q Q 3020 1d F OH Trichosporin_TS-B- * Ac U A G A U U Q U Lx U G Lx U P V U U Q 3021 1e Q F OH Trichosporin_TS-B-1f * Ac U A S A U U Q U Lx U G Lx U P V U U Q Q 3022 F OH Trichosporin_TS-B- * Ac U A G A U U Q U Lx U G Lx A P V U U Q 3023 1g Q F OH Trichosporin_TS-B- * Ac U A G A U U Q U Lx U G Lx U P V U Vx Q 3024 1h Q F OH Trichosporin_TS-B-Ia * Ac U A S A U U Q U L U G L U P V U U Q Q F 3025 OH Trichosporin_TS-B- * Ac U A A A U U Q U L U G L U P V U U Q Q F 3026 IIIa OH Trichosporin_TS-B- * Ac U A A A U U Q U I U G L U P V U A Q Q F 3027 IIIb OH Trichosporin_TS-B- * Ac U A A A A U Q U I U G L U P V U U Q Q F 3028 IIIc OH Trichosporin_TS-B- * Ac U A A A U U Q U V U G L U P V U U Q Q F 3029 IIId OH Trichosporin_TS-B- * Ac U A A A U U Q U L U G L U P V U J Q Q F 3030 IVb OH Trichosporin_TS-B- * Ac U A U A U U Q U V U G L U P V U U Q Q F 3031 IVc OH Trichosporin_TS-B- * Ac U A A A U U Q U V U G L U P V U J Q Q F 3032 IVd OH Trichosporin_TS-B-V * Ac U A A A U U Q U I U G L U P V U U Q Q F 3033 OH Trichosporin_TS-B- * Ac U A U A U U Q U I U G L U P V U U Q Q F 3034 VIa OH Trichosporin_TS-B- * Ac U A A A U U Q U I U G L U P V U J Q Q F 3035 VIb OH Trichotoxin_A-40 * Ac U G U L U E U U U A U U P L U J  Q V OH 3036 Trichotoxin_A-40_I * Ac U G U L U Q U U A A U U P L U U E V OH 3037 Trichotoxin_A-40_II * Ac U G U L U Q U U U A A U P L U U E V OH 3038 Trichotoxin_A-40_III  * Ac U G U L U Q U U A A U U P L U J E V OH 3039 Trichotoxin_A-40_IV * Ac U G U L U Q U U U A U U P L U U E V OH 3040 Trichotoxin_A-40_V * Ac U G U L U Q U U U A U U P L U J E V OH 3041 Trichotoxin_A-40_Va * Ac U A U L U Q U U U A U U P L U U E V OH 3042 Trichotoxin_A-50_E * Ac U G U L U Q U U U A A U P L U U Q V OH 3043 Trichotoxin_A-50_F * Ac U G U L U Q U U A A A U P L U J Q V OH 3044 Trichotoxin_A-50_G * Ac U G U L U Q U U U A A U P L U J Q V OH 3045 Trichotoxin_A-50_H * Ac U A U L U Q U U U A A U P L U J Q V OH 3046 Trichotoxin_A-50_I * Ac U G U L U Q U U U A U U P L U J Q V OH 3047 Trichotoxin_A-50_J * Ac U A U L U Q U U U A U U P L U J Q V OH 3048 Trichovirin-Ia * Ac U G A L A Q Vx V U G U U P L U U Q L 3049 OH Trichovirin-Ib * Ac U G A L U Q A V U G J U P L U U Q L OH 3050 Trichovirin-IIa * Ac U G A L A Q U V U G J U P L U U Q L OH 3051 Trichovirin-IIb * Ac U G A L U Q U V U G U U P L U U Q L OH 3052 Trichovirin-IIc * Ac U G A L U Q Vx V U G U U P L U U Q L 3053 OH Trichovirin-IIIa * Ac U G A L U Q J V U G U U P L U U Q L OH 3054 Trichovirin-IIIb * Ac U G A L J Q J U U G U U P L U U Q L OH 3055 Trichovirin-IVa * Ac U G A L J Q J V U G U U P L U U Q L OH 3056 Trichovirin-IVb * Ac U G A L U Q U V U G J U P L U U Q L OH 3057 Trichovirin-V * Ac U G A L U Q J V U G J U P L U U Q L OH 3058 Trichovirin-VIa * Ac U G A L U Q J L U G J U P L U U Q L OH 3059 Trichovirin-VIb * Ac U G A L J Q J V U G J U P L U U Q L OH 3060 Trikoningin_KA_V * Ac U G A U I Q U U U S L U P V U I Q Q L OH 3061 Trikoningin_KB_I * Oc U G V U G G V U G I L OH 3062 Trikoningin_KB_II * Oc J G V U G G V U G I L OH 3063 Tylopeptin_A * Ac W V U J A Q A U S U A L U Q L OH 3064 Tylopeptin_B * Ac W V U U A Q A U S U A L U Q L OH 3065 XR586 * Ac W J Q U I T U L U P Q U O J P F G OH 3066 Zervamicin_A-1-16 * Boc W I A U I V U L U P A U P U P F OCH3 3067 Zervamicin_ZIA * Ac W I E J V T U L U O Q U O U P F OH 3068 Zervamicin_ZIB * Ac W V E J I T U L U O Q U O U P F OH 3069 Zervamicin_ZIB′ * Ac W I E U I T U L U O Q U O U P F OH 3070 Zervamicin_ZIC * Ac W I E J I T U L U O Q U O U P F OH 3071 Zervamicin_ZII-1 * Ac W I Q U V T U L U O Q U O U P F OH 3072 Zervamicin_ZII-2 * Ac W I Q U I T U V U O Q U O U P F OH 3073 Zervamicin_ZII-3 * Ac W V Q U I T U L U O Q U O U P F OH 3074 Zervamicin_ZII-4 * Ac W I Q J V T U L U O Q U O U P F OH 3075 Zervamicin_ZII-5 * Ac W I Q J I T U V U O Q U O U P F OH 3076 Zervamicin_ZIIA * Ac W I Q U I T U L U O Q U O U P F OH 3077 Zervamicin_ZIIB * Ac W I Q J I T U L U O Q U O U P F OH 3078 CAMEL135 GWRLIKKILRVFKGL 3079 (CAM135) Novispirin G2 KNLRIIRKGIHIIKKY* 3080 B-33 FKKFWKWFRRF 3081 B-34 LKRFLKWFKRF 3082 B-35 KLFKRWKHLFR 3083 B-36 RLLKRFKHLFK 3084 B-37 FKTFLKWLHRF 3085 B-38 IKQLLHFFQRF 3086 B-39 KLLQTFKQIFR 3087 B-40 RILKELKNLFK 3088 B-41 LKQFVHFIHRF 3089 B-42 VKTLLHIFQRF 3090 B-43 KLVEQLKEIFR 3091 B-44 RVLQEIKQILK 3092 B-45 VKNLAELVHRF 3093 B-46 ATHLLHALQRF 3094 B-47 KLAENVKEILR 3095 B-48 RALHEAKEALK 3096 B-49 FHYFWHWFHRF 3097 B-50 LYHFLHWFQRF 3098 B-51 YLFQTWQHLFR 3099 B-52 YLLTEFQHLFK 3100 B-53 FKTFLQWLHRF 3101 B-54 IKTLLHFFQRF 3102 B-55 KLLQTFNQIFR 3103 B-56 TILQSLKNIFK 3104 B-57 LKQFVKFIHRF 3105 B-58 VKQLLKIFNRF 3106 B-59 KLVQQLKNIFR 3107 B-60 RVLNQVKQILK 3108 B-61 VKKLAKLVRRF 3109 B-62 AKRLLKVLKRF 3110 B-63 KLAQKVKRVLR 3111 B-64 RALKRIKHVLK 3112 1C-1 RRRRWWW 3113 1C-2 RRWWRRW 3114 1C-3 RRRWWWR 3115 1C-4 RWRWRWR 3116 2C-1 RRRFWWR 3117 2C-2 RRWWRRF* 3118 2C-3 RRRWWWF* 3119 2C-4 RWRWRWF* 3120 3C-1 RRRRWWK 3121 3C-2 RRWWRRK 3122 3C-3 RRRWWWK 3123 3C-4 RWRWRWK 3124 4C-1 RRRKWWK 3125 4C-2 RRWKRRK 3126 4C-3 RRRKWWK 3127 4C-4 RWRKRWK 3128 a-3 LHLLHQLLHLLHQF* 3129 a-4 AQAAHQAAHAAHQF* 3130 a-5 KLKKLLKKLKKLLK 3131 a-6 LKLLKKLLKLLKKF* 3132 a-7 LQLLKQLLKLLKQF* 3133 a-8 AQAAKQAAKAAKQF* 3134 a-9 RWRRWWRHFHHFFH* 3135 a-10 KLKKLLKRWRRWWR 3136 a-11 RWRRLLKKLHHLLH* 3137 a-12 KLKKLLKHLHHLLH* 3138 BD-1 FVF RHK WVW KHR FLF 3139 BD-2 VFI HRH VWV HKH VLF 3140 BD-3 WR WR AR WR WR LR WR F 3141 BD-4 WR IH LR AR LH VK FR F 3142 BD-5 LR IH AR FK VH IR LK F 3143 BD-6 FH IK FR VH LK VR FH F 3144 BD-7 FH VK IH FR LH VK FH F 3145 BD-8 LH IH AH FH VH IH LH F 3146 BD-9 FK IH FR LK VH IR FK F 3147 BD-10 FK AH IR FK LR VK FH F 3148 BD-11 LK AK IK FK VK LK IK F 3149 BD-12 WIW KHK FL HRH FLF 3150 BD-13 VFL HRH VI KHK LVF 3151 BD-14 FL HKH VL RHR IVF 3152 BD-15 VF KHK IV HRH ILF 3153 BD-16 FLF KH LFL HR IFF 3154 BD-17 LF KH ILI HR VIF 3155 BD-18 FL HKH LF KHK LF 3156 BD-19 VF RHR FI HRH VF 3157 BD-20 FI HK LV HKH VLF 3158 BD-21 VL RH LF RHR IVF 3159 BD-22 LV HK LIL RH LLF 3160 BD-23 VF KR VLI HK LIF 3161 BD-24 IV RK FLF RHK VF 3162 BD-25 VL KH VIA HKR LF 3163 BD-26 FI RK FLF KH LF 3164 BD-27 VI RH VWV RK LF 3165 BD-28 FLF RHR F RHR LVF 3166 BD-29 LFL HKH A KHK FLF 3167 BD-30 F KHK F KHK FIF 3168 BD-31 L RHR L RHR LIF 3169 BD-32 LIL K FLF K FVF 3170 BD-33 VLI R ILV R VIF 3171 BD-34 F RHR F RHR F 3172 BD-35 L KHK L KHK F 3173 BD-36 F K F KHK LIF 3174 BD-37 L R L RHR VLF 3175 BD-38 F K FLF K FLF 3176 BD-39 L R LFL R WLF 3177 BD-40 F K FLF KHK F 3178 BD-41 L R LFL RHR F 3179 BD-42 F K FLF K F 3180 BD-43 L R LFL R F 3181 AA-1 HHFFHHFHHFFHHF* 3182 AA-2 FHFFHHFFHFFHHF* 3183 AA-3 KLLK-GAT-FHFFHHFFHFFHHF 3184 AA-4 KLLK-FHFFHHFFHFFHHF 3185 AA-5 FHFFHHFFHFFHHFKLLK 3186 RIP YSPWTNF* 3187 Lariatin A c(Gly-Ser-Gln-Leu-Val-Tyr-Arg-Glu)-Trp-Val- 3188 (anti-mycobacteria) Gly-His-Ser-Asn-Val-Ile-Lys-Pro Lariatin B c(Gly-Ser-Gln-Leu-Val-Tyr-Arg-Glu)-Trp-Val- 3189 (anti-mycobacteria) Gly-His-Ser-Asn-Val-Ile-Lys-Gly-Pro-Pro Abreviations: U - Aminoisobutyric Acid (Aib); J - Isovaline (Iva); O - Hydroxyproline (Hyp); Z - Ethylnorvaline (EtNor); x or xx means L or I at that position; Ac - optionally acetylatedN-term; OH, OCH3 - optional C-term; Alkane long chains are noted in brackets; * optionally amidated C-terminus. Where protecting groups are shown, the gropus are optional. Conversely any of the peptides shown without protecting groups can, optionally bear one or more protecting groups. Where peptides are shown circularized, linear forms are also contemplated. Conversely, where linear peptides are shown circularlized versions are also contemplated.

In certain embodiments the antimicrobial peptide consists of or comprises the amino acid sequence of LL-37 (LLGDFFRK SKEKIGKEFKRIVQRIKD FLRNL VPRTES, SEQ ID NO:3190) or a variant of LL-37. LL-37 is a cathelicidin anti-microbial corresponding to amino acids 134-170 of the human cationic antimicrobial protein 18 (hCAP18). In certain embodiments the antimicrobial peptide consists of or comprises the amino acid sequence of an LL-37 variant as described in U.S. Patent Publication No: 2009/0156499 A1). Illustrative variants comprise or consist of the amino acid sequence having at least 90%, 95%, or 98% sequence identity with the amino acid sequence FKRIVQRIKDFLRX₁ (SEQ ID NO:3191), where X₁ is selected from the group consisting of 0, 1, 2, 3, 4, 5, 6, 7, and 8 amino acids. In certain embodiments illustrative variants comprise or consist of the amino acid sequence having at least 90%, 95%, or 98% sequence identity with the amino acid sequence X₁RLFDKIRQVIRKFX₂ (SEQ ID NO:3192) where X₁ is 0, 1, 2, 3, 4, 5, 6, 7, or 8 amino acids and X₂ is 0, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, or 16 amino acids.

In certain embodiments the antimicrobial peptide consists of or comprises the amino acid sequence of an LL-37 variant shown in Table 15.

TABLE 15 LL-37 peptide and variants. SEQ ID Amino acid sequence ID NO LL-37 LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNL 3193 VPRTES Cys-LL-37 CLLGDFFRKSKEKIGKEFKRIVQRIKDFLRN 3194 LVPRTES LL-37(17-32) FKRIVQRIKDFLRNLV 3195 Cys-LL-37-Cys CLLGDFFRKSKEKIGKEFKRIVQRIKDFLRN 3196 LVPRTESC LL-37FK-13 FKRIVQRIKDFLR 3197 LL-37FKR FKRIVQRIKDFLRNLVPRTES 3198 LL-37GKE GKEFKRIVQRIKDFLRNLVPR 3199 LL-37KRI KRIVQRIKDFLRNLVPRTES 3200 LL-37LLG LLGDFFRKSKEKIGKEFKRIV 3201 LL-37RKS RKSKEKIGKEFKRIVQRIKDFLRNLVPRTES 3202 LL-37SKE SKEKIGKEFKRIVQRIKDFLR 3203 LL-37-Cys LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNL 3204 VPRTESC

A number of antimicrobial peptides are also disclosed in U.S. Pat. Nos. 7,271,239, 7,223,840, 7,176,276, 6,809,181, 6,699,689, 6,420,116, 6,358,921, 6,316,594, 6,235,973, 6,183,992, 6,143,498, 6,042,848, 6,040,291, 5,936,063, 5,830,993, 5,428,016, 5,424,396, 5,032,574, 4,623,733, which are incorporated herein by reference for the disclosure of particular antimicrobial peptides.

v. Ligands.

In certain embodiments the effector can comprise one or more ligands, epitope tags, and/or antibodies. In certain embodiments preferred ligands and antibodies include those that bind to surface markers on immune cells. Chimeric moieties utilizing such antibodies as effector molecules act as bifunctional linkers establishing an association between the immune cells bearing binding partner for the ligand or antibody and the target microorganism(s).

The terms “epitope tag” or “affinity tag” are used interchangeably herein, and used refers to a molecule or domain of a molecule that is specifically recognized by an antibody or other binding partner. The term also refers to the binding partner complex as well. Thus, for example, biotin or a biotin/avidin complex are both regarded as an affinity tag. In addition to epitopes recognized in epitope/antibody interactions, affinity tags also comprise “epitopes” recognized by other binding molecules (e.g. ligands bound by receptors), ligands bound by other ligands to form heterodimers or homodimers, His₆ bound by Ni-NTA, biotin bound by avidin, streptavidin, or anti-biotin antibodies, and the like.

Epitope tags are well known to those of skill in the art. Moreover, antibodies specific to a wide variety of epitope tags are commercially available. These include but are not limited to antibodies against the DYKDDDDK (SEQ ID NO:3205) epitope, c-myc antibodies (available from Sigma, St. Louis), the HNK-1 carbohydrate epitope, the HA epitope, the HSV epitope, the His₄ (SEQ ID NO:3206), His_(s) (SEQ ID NO:3207), and His₆ (SEQ ID NO:3208) epitopes that are recognized by the His epitope specific antibodies (see, e.g., Qiagen), and the like. In addition, vectors for epitope tagging proteins are commercially available. Thus, for example, the pCMV-Tag1 vector is an epitope tagging vector designed for gene expression in mammalian cells. A target gene inserted into the pCMV-Tag1 vector can be tagged with the FLAG® epitope (N-terminal, C-terminal or internal tagging), the c-myc epitope (C-terminal) or both the FLAG (N-terminal) and c-myc (C-terminal) epitopes.

vi. Lipids and Liposomes.

In certain embodiments the effectors comprise one or more microparticles or nanoparticles that can be loaded with an effector agent (e.g., a pharmaceutical, a label, etc.). In certain embodiments the microparticles or nanoparticles are lipidic particles. Lipidic particles are microparticles or nanoparticles that include at least one lipid component forming a condensed lipid phase. Typically, a lipidic nanoparticle has preponderance of lipids in its composition. Various condensed lipid phases include solid amorphous or true crystalline phases; isomorphic liquid phases (droplets); and various hydrated mesomorphic oriented lipid phases such as liquid crystalline and pseudocrystalline bilayer phases (L-alpha, L-beta, P-beta, Lc), interdigitated bilayer phases, and nonlamellar phases (see, e.g., The Structure of Biological Membranes, ed. by P. Yeagle, CRC Press, Bora Raton, Fla., 1991). Lipidic microparticles include, but are not limited to a liposome, a lipid-nucleic acid complex, a lipid-drug complex, a lipid-label complex, a solid lipid particle, a microemulsion droplet, and the like. Methods of making and using these types of lipidic microparticles and nanoparticles, as well as attachment of affinity moieties, e.g., antibodies, to them are known in the art (see, e.g., U.S. Pat. Nos. 5,077,057; 5,100,591; 5,616,334; 6,406,713; 5,576,016; 6,248,363; Bondi et al. (2003) Drug Delivery 10: 245-250; Pedersen et al., (2006) Eur. J. Pharm. Biopharm. 62: 155-162, 2006 (solid lipid particles); U.S. Pat. Nos. 5,534,502; 6,720,001; Shiokawa et al. (2005) Clin. Cancer Res. 11: 2018-2025 (microemulsions); U.S. Pat. No. 6,071,533 (lipid-nucleic acid complexes), and the like).

A liposome is generally defined as a particle comprising one or more lipid bilayers enclosing an interior, typically an aqueous interior. Thus, a liposome is often a vesicle formed by a bilayer lipid membrane. There are many methods for the preparation of liposomes. Some of them are used to prepare small vesicles (d<0.05 micrometer), some for larger vesicles (d>0.05 micrometer). Some are used to prepare multilamellar vesicles, some for unilamellar ones. Methods for liposome preparation are exhaustively described in several review articles such as Szoka and Papahadjopoulos (1980) Ann. Rev. Biophys. Bioeng., 9: 467, Deamer and Uster (1983) Pp. 27-51 In: Liposomes, ed. M. J. Ostro, Marcel Dekker, New York, and the like.

In various embodiments the liposomes include a surface coating of a hydrophilic polymer chain. “Surface-coating” refers to the coating of any hydrophilic polymer on the surface of liposomes. The hydrophilic polymer is included in the liposome by including in the liposome composition one or more vesicle-forming lipids derivatized with a hydrophilic polymer chain. In certain embodiments, vesicle-forming lipids with diacyl chains, such as phospholipids, are preferred. One illustrative phospholipid is phosphatidylethanolamine (PE), which contains a reactive amino group convenient for coupling to the activated polymers. One illustrative PE is distearoyl PE (DSPE). Another example is non-phospholipid double chain amphiphilic lipids, such as diacyl- or dialkylglycerols, derivatized with a hydrophilic polymer chain.

In certain embodiments a hydrophilic polymer for use in coupling to a vesicle forming lipid is polyethyleneglycol (PEG), preferably as a PEG chain having a molecular weight between 1,000-10,000 Daltons, more preferably between 1,000-5,000 Daltons, most preferably between 2,000-5,000 Daltons. Methoxy or ethoxy-capped analogues of PEG are also useful hydrophilic polymers, commercially available in a variety of polymer sizes, e.g., 120-20,000 Daltons.

Other hydrophilic polymers that can be suitable include, but are not limited to polylactic acid, polyglycolic acid, polyvinylpyrrolidone, polymethyloxazoline, polyethyloxazoline, polyhydroxypropyl methacrylamide, polymethacrylamide, polydimethylacrylamide, and derivatized celluloses, such as hydroxymethylcellulose or hydroxyethylcellulose.

Preparation of lipid-polymer conjugates containing these polymers attached to a suitable lipid, such as PE, have been described.

The liposomes can, optionally be prepared for attachment to one or more targeting moieties described herein. Here the lipid component included in the liposomes would include either a lipid derivatized with the targeting moiety, or a lipid having a polar-head chemical group, e.g., on a linker, that can be derivatized with the targeting moiety in preformed liposomes, according to known methods.

Methods of functionalizing lipids and liposomes with affinity moieties such as antibodies are well known to those of skill in the art (see, e.g., DE 3,218,121; Epstein et al. (1985) Proc. Natl. Acad. Sci., USA, 82:3688 (1985); Hwang et al. (1980) Proc. Natl. Acad. Sci., USA, 77: 4030; EP 52,322; EP 36,676; EP 88,046; EP 143,949; EP 142,641; Japanese patent application 83-118008; U.S. Pat. Nos. 4,485,045 and 4,544,545; and EP 102,324, all of which are incorporated herein by reference).

vii. Agents that Physically Disrupt the Extracellular Matrix within a Community of Microorganisms

In certain embodiments, peptides can be coupled to agents that physically disrupt the extracellular matrix within a community of microorganisms, for example a biofilm. In certain preferred embodiments, such an agent could be a bacterial cell-wall degrading enzyme, for example SAL-2, or any species of glycosidase, alginase, peptidase, proteinase, lipase, or DNA or RNA degrading enzyme or compound, for example rhRNase. Disruption of extracellular matrix of biofilms can result in clearance and therapeutic benefit.

Peptides can also be attached to antimicrobial proteins, such as Protein Inhibitor C or Colicin, or fragments thereof, for example the IIa domain of Colicin, or the heparin-binding domain of Protein Inhibitor C.

viii. Polymeric Microparticles and/or Nanoparticles.

In certain embodiments the effector(s) comprise polymeric microparticles and/or nanoparticles and/or micelles.

Microparticle and nanoparticle-based drug delivery systems have considerable potential for treatment of various microorganisms. Technological advantages of polymeric microparticles or nanoparticles used as drug carriers are high stability, high carrier capacity, feasibility of incorporation of both hydrophilic and hydrophobic substances, and feasibility of variable routes of administration, including oral application and inhalation. Polymeric nanoparticles can also be designed to allow controlled (sustained) drug release from the matrix. These properties of nanoparticles enable improvement of drug bioavailability and reduction of the dosing frequency.

Polymeric nanoparticles are typically micron or submicron (<1 μm) colloidal particles. This definition includes monolithic nanoparticles (nanospheres) in which the drug is adsorbed, dissolved, or dispersed throughout the matrix and nanocapsules in which the drug is confined to an aqueous or oily core surrounded by a shell-like wall. Alternatively, in certain embodiments, the drug can be covalently attached to the surface or into the matrix.

Polymeric microparticles and nanoparticles are typically made from biocompatible and biodegradable materials such as polymers, either natural (e.g., gelatin, albumin) or synthetic (e.g., polylactides, polyalkylcyanoacrylates), or solid lipids. In the body, the drug loaded in nanoparticles is usually released from the matrix by diffusion, swelling, erosion, or degradation. One commonly used material is poly(lactide-co-glycolide) (PLG).

Methods of fabricating and loading polymeric nanoparticles or microparticles are well known to those of skill in the art. Thus, for example, Matsumoto et al. (1999) Intl. J. Pharmaceutics, 185: 93-101 teaches the fabrication of poly(L-lactide)-poly(ethylene glycol)-poly(L-lactide) nanoparticles, Chawla et al. (2002) Intl. J. Pharmaceutics 249: 127-138, teaches the fabrication and use of poly(e-caprolactone) nanoparticles delivery of tamifoxen, and Bodmeier et al. (1988) Intl. J. Pharmaceutics, 43: 179-186, teaches the preparation of poly(D,L-lactide) microspheres using a solvent evaporation method.” Intl. J. Pharmaceutics, 1988, 43, 179-186. Other nanoparticle formulations are described, for example, by Williams et al. (2003) J. Controlled Release, 91: 167-172; Leroux et al. (1996) J. Controlled Release, 39: 339-350; Soppimath et al. (2001) J. Controlled Release, 70:1-20; Brannon-Peppas (1995) Intl. J. Pharmaceutics, 116: 1-9; and the like.

C) Peptide Preparation.

The peptides described herein can be chemically synthesized using standard chemical peptide synthesis techniques or, particularly where the peptide does not comprise “D” amino acid residues, the peptide can be recombinantly expressed. Where the “D” polypeptides are recombinantly expressed, a host organism (e.g. bacteria, plant, fungal cells, etc.) can be cultured in an environment where one or more of the amino acids is provided to the organism exclusively in a D form. Recombinantly expressed peptides in such a system then incorporate those D amino acids.

In certain embodiments, D amino acids can be incorporated in recombinantly expressed peptides using modified amino acyl-tRNA synthetases that recognize D-amino acids.

In certain embodiments the peptides are chemically synthesized by any of a number of fluid or solid phase peptide synthesis techniques known to those of skill in the art. Solid phase synthesis in which the C-terminal amino acid of the sequence is attached to an insoluble support followed by sequential addition of the remaining amino acids in the sequence is a preferred method for the chemical synthesis of the polypeptides of this invention. Techniques for solid phase synthesis are well known to those of skill in the art and are described, for example, by Barany and Merrifield (1963) Solid-Phase Peptide Synthesis; pp. 3-284 in The Peptides: Analysis, Synthesis, Biology. Vol. 2: Special Methods in Peptide Synthesis, Part A.; Merrifield et al. (1963) J. Am. Chem. Soc., 85: 2149-2156, and Stewart et al. (1984) Solid Phase Peptide Synthesis, 2nd ed. Pierce Chem. Co., Rockford, Ill.

In one embodiment, the peptides can be synthesized by the solid phase peptide synthesis procedure using a benzhyderylamine resin (Beckman Bioproducts, 0.59 mmol of NH₂/g of resin) as the solid support. The COOH terminal amino acid (e.g., t-butylcarbonyl-Phe) is attached to the solid support through a 4-(oxymethyl)phenacetyl group. This is a more stable linkage than the conventional benzyl ester linkage, yet the finished peptide can still be cleaved by hydrogenation. Transfer hydrogenation using formic acid as the hydrogen donor can be used for this purpose.

It is noted that in the chemical synthesis of peptides, particularly peptides comprising D amino acids, the synthesis usually produces a number of truncated peptides in addition to the desired full-length product. Thus, the peptides are typically purified using, e.g., HPLC.

D-amino acids, beta amino acids, non-natural amino acids, and the like can be incorporated at one or more positions in the peptide simply by using the appropriately derivatized amino acid residue in the chemical synthesis. Modified residues for solid phase peptide synthesis are commercially available from a number of suppliers (see, e.g., Advanced Chem Tech, Louisville; Nova Biochem, San Diego; Sigma, St Louis; Bachem Calif. Inc., Torrance, etc.). The D-form and/or otherwise modified amino acids can be completely omitted or incorporated at any position in the peptide as desired. Thus, for example, in certain embodiments, the peptide can comprise a single modified acid, while in other embodiments, the peptide comprises at least two, generally at least three, more generally at least four, most generally at least five, preferably at least six, more preferably at least seven or even all modified amino acids. In certain embodiments, essentially every amino acid is a D-form amino acid.

As indicated above, the peptides and/or fusion proteins of this invention can also be recombinantly expressed. Accordingly, in certain embodiments, the antimicrobial peptides and/or targeting moieties, and/or fusion proteins of this invention are synthesized using recombinant expression systems. Generally this involves creating a DNA sequence that encodes the desired peptide or fusion protein, placing the DNA in an expression cassette under the control of a particular promoter, expressing the peptide or fusion protein in a host, isolating the expressed peptide or fusion protein and, if required, renaturing the peptide or fusion protein.

DNA encoding the peptide(s) or fusion protein(s) described herein can be prepared by any suitable method as described above, including, for example, cloning and restriction of appropriate sequences or direct chemical synthesis.

This nucleic acid can be easily ligated into an appropriate vector containing appropriate expression control sequences (e.g. promoter, enhancer, etc.), and, optionally, containing one or more selectable markers (e.g. antibiotic resistance genes).

The nucleic acid sequences encoding the peptides or fusion proteins described herein can be expressed in a variety of host cells, including, but not limited to, E. coli, other bacterial hosts, yeast, fungus, and various higher eukaryotic cells such as insect cells (e.g. SF3), the COS, CHO and HeLa cells lines and myeloma cell lines. The recombinant protein gene will typically be operably linked to appropriate expression control sequences for each host. For E. coli this can include a promoter such as the T7, tip, or lambda promoters, a ribosome binding site and preferably a transcription termination signal. For eukaryotic cells, the control sequences can include a promoter and often an enhancer (e.g., an enhancer derived from immunoglobulin genes, SV40, cytomegalovirus, etc.), and a polyadenylation sequence, and may include splice donor and acceptor sequences.

The plasmids can be transferred into the chosen host cell by well-known methods such as calcium chloride transformation for E. coli and calcium phosphate treatment or electroporation for mammalian cells. Cells transformed by the plasmids can be selected by resistance to antibiotics conferred by genes contained on the plasmids, such as the amp, gpt, neo and hyg genes.

Once expressed, the recombinant peptide(s) or fusion protein(s) can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, gel electrophoresis and the like (see, generally, R. Scopes, (1982) Protein Purification, Springer-Verlag, N.Y.; Deutscher (1990) Methods in Enzymology Vol. 182: Guide to Protein Purification., Academic Press, Inc. N.Y.). Substantially pure compositions of at least about 90 to 95% homogeneity are preferred, and 98 to 99% or more homogeneity are most preferred.

One of skill in the art would recognize that after chemical synthesis, biological expression, or purification, the peptide(s) or fusion protein(s) may possess a conformation substantially different than desired native conformation. In this case, it may be necessary to denature and reduce the peptide or fusion protein and then to cause the molecule to re-fold into the preferred conformation. Methods of reducing and denaturing proteins and inducing re-folding are well known to those of skill in the art (see, e.g., Debinski et al. (1993) J. Biol. Chem., 268: 14065-14070; Kreitman and Pastan (1993) Bioconjug. Chem., 4: 581-585; and Buchner, et al., (1992) Anal. Biochem., 205: 263-270). Debinski et al., for example, describes the denaturation and reduction of inclusion body proteins in guanidine-DTE. The protein is then refolded in a redox buffer containing oxidized glutathione and L-arginine.

One of skill would recognize that modifications can be made to the peptide(s) and/or fusion protein(s) proteins without diminishing their biological activity. Some modifications may be made to facilitate the cloning, expression, or incorporation of the targeting molecule into a fusion protein. Such modifications are well known to those of skill in the art and include, for example, a methionine added at the amino terminus to provide an initiation site, or additional amino acids (e.g., poly His) placed on either terminus to create conveniently located restriction sites or termination codons or purification sequences.

D) Joining Targeting Moieties to Effectors.

i. Chemical Conjugation.

Chimeric moieties are formed by joining one or more of the targeting moieties described herein to one or more effectors. In certain embodiments the targeting moieties are attached directly to the effector(s) via naturally occurring reactive groups or the targeting moiety and/or the effector(s) can be functionalized to provide such reactive groups.

In various embodiments the targeting moieties are attached to effector(s) via one or more linking agents. Thus, in various embodiments the targeting moieties and the effector(s) can be conjugated via a single linking agent or multiple linking agents. For example, the targeting moiety and the effector can be conjugated via a single multifunctional (e.g., bi-, tri-, or tetra-) linking agent or a pair of complementary linking agents. In another embodiment, the targeting moiety and the effector are conjugated via two, three, or more linking agents. Suitable linking agents include, but are not limited to, e.g., functional groups, affinity agents, stabilizing groups, and combinations thereof.

In certain embodiments the linking agent is or comprises a functional group. Functional groups include monofunctional linkers comprising a reactive group as well as multifunctional crosslinkers comprising two or more reactive groups capable of forming a bond with two or more different functional targets (e.g., labels, proteins, macromolecules, semiconductor nanocrystals, or substrate). In some preferred embodiments, the multifunctional crosslinkers are heterobifunctional crosslinkers comprising two or more different reactive groups.

Suitable reactive groups include, but are not limited to thiol (—SH), carboxylate (COOH), carboxyl (—COOH), carbonyl, amine (NH₂), hydroxyl (—OH), aldehyde (—CHO), alcohol (ROH), ketone (R₂CO), active hydrogen, ester, sulfhydryl (SH), phosphate (—PO₃), or photoreactive moieties. Amine reactive groups include, but are not limited to e.g., isothiocyanates, isocyanates, acyl azides, NHS esters, sulfonyl chlorides, aldehydes and glyoxals, epoxides and oxiranes, carbonates, arylating agents, imidoesters, carbodiimides, and anhydrides. Thiol-reactive groups include, but are not limited to e.g., haloacetyl and alkyl halide derivates, maleimides, aziridines, acryloyl derivatives, arylating agents, and thiol-disulfides exchange reagents. Carboxylate reactive groups include, but are not limited to e.g., diazoalkanes and diazoacetyl compounds, such as carbonyldiimidazoles and carbodiimides. Hydroxyl reactive groups include, but are not limited to e.g., epoxides and oxiranes, carbonyldiimidazole, oxidation with periodate, N,N′-disuccinimidyl carbonate or N-hydroxylsuccimidyl chloroformate, enzymatic oxidation, alkyl halogens, and isocyanates. Aldehyde and ketone reactive groups include, but are not limited to e.g., hydrazine derivatives for schiff base formation or reduction amination. Active hydrogen reactive groups include, but are not limited to e.g., diazonium derivatives for mannich condensation and iodination reactions. Photoreactive groups include, but are not limited to e.g., aryl azides and halogenated aryl azides, benzophenones, diazo compounds, and diazirine derivatives.

Other suitable reactive groups and classes of reactions useful in forming chimeric moieties include those that are well known in the art of bioconjugate chemistry. Currently favored classes of reactions available with reactive chelates are those which proceed under relatively mild conditions. These include, but are not limited to, nucleophilic substitutions (e.g., reactions of amines and alcohols with acyl halides, active esters), electrophilic substitutions (e.g., enamine reactions), and additions to carbon-carbon and carbon-heteroatom multiple bonds (e.g., Michael reaction, Diels-Alder addition). These and other useful reactions are discussed in, for example, March (1985) Advanced Organic Chemistry, 3rd Ed., John Wiley & Sons, New York, Hermanson (1996) Bioconjugate Techniques, Academic Press, San Diego; and Feeney et al. (1982) Modification of Proteins; Advances in Chemistry Series, Vol. 198, American Chemical Society, Washington, D.C.

In certain embodiments, the linking agent comprises a chelator. For example, the chelator comprising the molecule, DOTA (DOTA=1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane), can readily be labeled with a radiolabel, such as Gd³⁺ and ⁶⁴Cu, resulting in Gd³⁺-DOTA and ⁶⁴Cu-DOTA respectively, attached to the targeting moiety. Other suitable chelates are known to those of skill in the art, for example, 1,4,7-triazacyclononane-N,N′,N″-triacetic acid (NOTA) derivatives being among the most well known (see, e.g., Lee et al. (1997) Nucl Med Biol. 24: 2225-23019).

A “linker” or “linking agent” as used herein, is a molecule that is used to join two or more molecules. In certain embodiments the linker is typically capable of forming covalent bonds to both molecule(s) (e.g., the targeting moiety and the effector). Suitable linkers are well known to those of skill in the art and include, but are not limited to, straight or branched-chain carbon linkers, heterocyclic carbon linkers, or peptide linkers. In certain embodiments the linkers can be joined to the constituent amino acids through their side groups (e.g., through a disulfide linkage to cysteine). However, in certain embodiments, the linkers will be joined to the alpha carbon amino and carboxyl groups of the terminal amino acids.

A bifunctional linker having one functional group reactive with a group on one molecule (e.g., a targeting peptide), and another group reactive on the other molecule (e.g., an antimicrobial peptide), can be used to form the desired conjugate. Alternatively, derivatization can be performed to provide functional groups. Thus, for example, procedures for the generation of free sulfhydryl groups on peptides are also known (See U.S. Pat. No. 4,659,839).

In certain embodiments the linking agent is a heterobifunctional crosslinker comprising two or more different reactive groups that form a heterocyclic ring that can interact with a peptide. For example, a heterobifunctional crosslinker such as cysteine may comprise an amine reactive group and a thiol-reactive group can interact with an aldehyde on a derivatized peptide. Additional combinations of reactive groups suitable for heterobifunctional crosslinkers include, for example, amine- and sulfhydryl reactive groups; carbonyl and sulfhydryl reactive groups; amine and photoreactive groups; sulfhydryl and photoreactive groups; carbonyl and photoreactive groups; carboxylate and photoreactive groups; and arginine and photoreactive groups. In one embodiment, the heterobifunctional crosslinker is SMCC.

Many procedures and linker molecules for attachment of various molecules to peptides or proteins are known (see, e.g., European Patent Application No. 188,256; U.S. Pat. Nos. 4,671,958, 4,659,839, 4,414,148, 4,699,784; 4,680,338; 4,569,789; and 4,589,071; and Borlinghaus et al. (1987) Cancer Res. 47: 4071-4075). Illustrative linking protocols are provided herein in Examples 2 and 3.

ii. Fusion Proteins.

In certain embodiments where the targeting moiety and effector are both peptides or both comprise peptides, the chimeric moiety can be chemically synthesized or recombinantly expressed as a fusion protein (i.e., a chimeric fusion protein).

In certain embodiments the chimeric fusion proteins are synthesized using recombinant DNA methodology. Generally this involves creating a DNA sequence that encodes the fusion protein, placing the DNA in an expression cassette under the control of a particular promoter, expressing the protein in a host, isolating the expressed protein and, if required, renaturing the protein.

DNA encoding the fusion proteins can be prepared by any suitable method, including, for example, cloning and restriction of appropriate sequences or direct chemical synthesis by methods such as the phosphotriester method of Narang et al. (1979) Meth. Enzymol. 68: 90-99; the phosphodiester method of Brown et al. (1979) Meth. Enzymol. 68: 109-151; the diethylphosphoramidite method of Beaucage et al. (1981) Tetra. Lett., 22: 1859-1862; and the solid support method of U.S. Pat. No. 4,458,066.

Chemical synthesis produces a single stranded oligonucleotide. This can be converted into double stranded DNA by hybridization with a complementary sequence or by polymerization with a DNA polymerase using the single strand as a template. One of skill would recognize that while chemical synthesis of DNA is limited to sequences of about 100 bases, longer sequences can be obtained by the ligation of shorter sequences.

Alternatively, subsequences can be cloned and the appropriate subsequences cleaved using appropriate restriction enzymes. The fragments can then be ligated to produce the desired DNA sequence.

In certain embodiments, DNA encoding fusion proteins of the present invention may be cloned using DNA amplification methods such as polymerase chain reaction (PCR). Thus, for example, the nucleic acid encoding a targeting antibody, a targeting peptide, and the like is PCR amplified, using a sense primer containing the restriction site for NdeI and an antisense primer containing the restriction site for HindIII. This produces a nucleic acid encoding the targeting sequence and having terminal restriction sites. Similarly an effector and/or effector/linker/spacer can be provided having complementary restriction sites. Ligation of sequences and insertion into a vector produces a vector encoding the fusion protein.

While the targeting moieties and effector(s) can be directly joined together, one of skill will appreciate that they can be separated by a peptide spacer/linker consisting of one or more amino acids. Generally the spacer will have no specific biological activity other than to join the proteins or to preserve some minimum distance or other spatial relationship between them. However, the constituent amino acids of the spacer may be selected to influence some property of the molecule such as the folding, net charge, or hydrophobicity.

The nucleic acid sequences encoding the fusion proteins can be expressed in a variety of host cells, including E. coli, other bacterial hosts, yeast, and various higher eukaryotic cells such as the COS, CHO and HeLa cells lines and myeloma cell lines. The recombinant protein gene will be operably linked to appropriate expression control sequences for each host. For E. coli this includes a promoter such as the T7, trp, or lambda promoters, a ribosome binding site and preferably a transcription termination signal. For eukaryotic cells, the control sequences will include a promoter and preferably an enhancer derived from immunoglobulin genes, SV40, cytomegalovirus, etc., and a polyadenylation sequence, and may include splice donor and acceptor sequences.

The plasmids can be transferred into the chosen host cell by well-known methods such as calcium chloride transformation for E. coli and calcium phosphate treatment or electroporation for mammalian cells. Cells transformed by the plasmids can be selected by resistance to antibiotics conferred by genes contained on the plasmids, such as the amp, gpt, neo and hyg genes.

Once expressed, the recombinant fusion proteins can be purified according to standard procedures of the art, including ammonium sulfate precipitation, affinity columns, column chromatography, gel electrophoresis and the like (see, generally, R. Scopes (1982) Protein Purification, Springer-Verlag, N.Y.; Deutscher (1990) Methods in Enzymology Vol. 182: Guide to Protein Purification., Academic Press, Inc. N.Y.). Substantially pure compositions of at least about 90 to 95% homogeneity are preferred, and 98 to 99% or more homogeneity are most preferred for pharmaceutical uses. Once purified, partially or to homogeneity as desired, the polypeptides may then be used therapeutically.

One of skill in the art would recognize that after chemical synthesis, biological expression, or purification, the fusion protein may possess a conformation substantially different than the native conformations of the constituent polypeptides. In this case, it may be necessary to denature and reduce the polypeptide and then to cause the polypeptide to re-fold into the preferred conformation. Methods of reducing and denaturing proteins and inducing re-folding are well known to those of skill in the art (See, Debinski et al. (1993) J. Biol. Chem., 268: 14065-14070; Kreitman and Pastan (1993) Bioconjug. Chem., 4: 581-585; and Buchner, et al. (1992) Anal. Biochem., 205: 263-270).

One of skill would recognize that modifications can be made to the fusion proteins without diminishing their biological activity. Some modifications may be made to facilitate the cloning, expression, or incorporation of the targeting molecule into a fusion protein. Such modifications are well known to those of skill in the art and include, for example, a methionine added at the amino terminus to provide an initiation site, or additional amino acids placed on either terminus to create conveniently located restriction sites or termination codons.

As indicated above, in various embodiments a peptide linker/spacer is used to join the one or more targeting moieties to one or more effector(s). In various embodiments the peptide linker is relatively short, typically less than about 10 amino acids, preferably less than about 8 amino acids and more preferably about 3 to about 5 amino acids. Suitable illustrative linkers include, but are not limited to PSGSP ((SEQ ID NO:3209), ASASA (SEQ ID NO: 3210), or GGG. In certain embodiments longer linkers such as (GGGGS)₃ (SEQ ID NO:3211) can be used. Illustrative peptide linkers and other linkers are shown in Table 16.

TABLE 16 Illustrative peptide and non-peptide linkers. SEQ Linker ID NO: AAA GGG GGGG 3212 SGG GGSGGS 3213 SAT PYP PSPSP 3214 ASA ASASA 3215 PSPSP 3216 KKKK 3217 RRRR 3218 GGGGS 3219 GGGGS GGGGS 3220 GGGGS GGGGS GGGGS 3221 GGGGS GGGGS GGGGS GGGGS 3222 GGGGS GGGGS GGGGS GGGGS GGGGS 3223 GGGGS GGGGS GGGGS GGGGS GGGGS GGGGS 3224 2-nitrobenzene or O-nitrobenzyl Nitropyridyl disulfide Dioleoylphosphatidylethanolamine (DOPE) S-acetylmercaptosuccinic acid 1, 4, 7, 10-tetraazacyclododecane-1, 4, 7, 10-tetracetic acid (DOTA) β-glucuronide and β-glucuronide variants Poly(alkylacrylic acid) Benzene-based linkers (for example: 2,5-Bis(hexyloxy)-1,4-bis[2,5-bis(hexyloxy)- 4-formyl-phenylenevinylene]benzene) and like molecules Disulfide linkages Poly(amidoamine) or like dendrimers linking multiple target and killing peptides in one molecule Carbon nanotubes Hydrazone and hydrazone variant linkers PEG of any chain length Succinate, formate, acetate butyrate, other like organic acids Aldols, alcohols, or enols Peroxides alkane or alkene groups of any chain length One or more porphyrin or dye molecules containing free amide and carboxylic acid groups One or more DNA or RNA nucleotides, including polyamine and polycarboxyl- containing variants Inulin, sucrose, glucose, or other single, di or polysaccharides Linoleic acid or other polyunsaturated fatty acids Variants of any of the above linkers containing halogen or thiol groups (All amino-acid-based linkers could be L, D, combinations of L and D forms, β-form, and the like)

E) Multiple Targeting Moieties and/or Effectors.

As indicated above, in certain embodiments, the chimeric moieties described herein comprise multiple targeting moieties attached to a single effector or multiple effectors attached to a single targeting moiety, or multiple targeting moieties attached to multiple effectors.

Where the chimeric construct is a fusion protein this is easily accomplished by providing multiple domains that are targeting domains attached to one or more effector domains. FIG. 14 schematically illustrates a few, but not all, configurations. In various embodiments the multiple targeting domains and/or multiple effector domains can be attached to each other directly or can be separated by linkers (e.g., amino acid or peptide linkers as described above).

When the chimeric construct is a chemical conjugate linear or branched configurations (e.g., as illustrated in FIG. 14) are readily produced by using branched or multifunctional linkers and/or a plurality of different linkers.

F) Protecting Groups.

While the various peptides (e.g., targeting peptides, antimicrobial peptides, STAMPs) described herein may be shown with no protecting groups, in certain embodiments they can bear one, two, three, four, or more protecting groups. In various embodiments, the protecting groups can be coupled to the C- and/or N-terminus of the peptide(s) and/or to one or more internal residues comprising the peptide(s) (e.g., one or more R-groups on the constituent amino acids can be blocked). Thus, for example, in certain embodiments, any of the peptides described herein can bear, e.g., an acetyl group protecting the amino terminus and/or an amide group protecting the carboxyl terminus. One example of such a protected peptide is the 1845L6-21 STAMP having the amino acid sequence

(SEQ ID NO: 3225) KFINGVLSQFVLERKPYPKLFKFLRKHLL*, where the asterisk indicates an amidated carboxyl terminus. Of course, this protecting group can be can be eliminated and/or substituted with another protecting group as described herein.

Without being bound by a particular theory, it was discovered that addition of a protecting group, particularly to the carboxyl and in certain embodiments the amino terminus can improve the stability and efficacy of the peptide.

A wide number of protecting groups are suitable for this purpose. Such groups include, but are not limited to acetyl, amide, and alkyl groups with acetyl and alkyl groups being particularly preferred for N-terminal protection and amide groups being preferred for carboxyl terminal protection. In certain particularly preferred embodiments, the protecting groups include, but are not limited to alkyl chains as in fatty acids, propionyl, formyl, and others. Particularly preferred carboxyl protecting groups include amides, esters, and ether-forming protecting groups. In one preferred embodiment, an acetyl group is used to protect the amino terminus and an amide group is used to protect the carboxyl terminus. These blocking groups enhance the helix-forming tendencies of the peptides. Certain particularly preferred blocking groups include alkyl groups of various lengths, e.g., groups having the formula: CH₃—(CH₂)_(n)—CO— where n ranges from about 1 to about 20, preferably from about 1 to about 16 or 18, more preferably from about 3 to about 13, and most preferably from about 3 to about 10.

In certain embodiments, the protecting groups include, but are not limited to alkyl chains as in fatty acids, propionyl, formyl, and others. Particularly preferred carboxyl protecting groups include amides, esters, and ether-forming protecting groups. In one embodiment, an acetyl group is used to protect the amino terminus and/or an amino group is used to protect the carboxyl terminus (i.e., amidated carboxyl terminus). In certain embodiments blocking groups include alkyl groups of various lengths, e.g., groups having the formula: CH₃—(CH₂)_(n)—CO— where n ranges from about 3 to about 20, preferably from about 3 to about 16, more preferably from about 3 to about 13, and most preferably from about 3 to about 10.

In certain embodiments, the acid group on the C-terminal can be blocked with an alcohol, aldehyde or ketone group and/or the N-terminal residue can have the natural amide group, or be blocked with an acyl, carboxylic acid, alcohol, aldehyde, or ketone group.

Other protecting groups include, but are not limited to Fmoc, t-butoxycarbonyl (t-BOC), 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, xanthyl (Xan), trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), benzyloxy (BzlO), benzyl (Bzl), benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bom), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), Acetyl (Ac), and Trifluoroacetyl (TFA).

Protecting/blocking groups are well known to those of skill as are methods of coupling such groups to the appropriate residue(s) comprising the peptides of this invention (see, e.g., Greene et al., (1991) Protective Groups in Organic Synthesis, 2nd ed., John Wiley & Sons, Inc. Somerset, N.J.). In illustrative embodiment, for example, acetylation is accomplished during the synthesis when the peptide is on the resin using acetic anhydride. Amide protection can be achieved by the selection of a proper resin for the synthesis. For example, a rink amide resin can be used. After the completion of the synthesis, the semipermanent protecting groups on acidic bifunctional amino acids such as Asp and Glu and basic amino acid Lys, hydroxyl of Tyr are all simultaneously removed. The peptides released from such a resin using acidic treatment comes out with the n-terminal protected as acetyl and the carboxyl protected as NH₂ and with the simultaneous removal of all of the other protecting groups.

Where amino acid sequences are disclosed herein, amino acid sequences comprising, one or more protecting groups, e.g., as described above (or any other commercially available protecting groups for amino acids used, e.g., in boc or fmoc peptide synthesis) are also contemplated.

G) Peptide Circularization.

In certain embodiments the peptides described herein (e.g., AMPs, compound AMPs, STAMPs, etc.) are circularized/cyclized to produce cyclic peptides. Cyclic peptides, as contemplated herein, include head/tail, head/side chain, tail/side chain, and side chain/side chain cyclized peptides. In addition, peptides contemplated herein include homodet, containing only peptide bonds, and heterodet containing in addition disulfide, ester, thioester-bonds, or other bonds.

The cyclic peptides can be prepared using virtually any art-known technique for the preparation of cyclic peptides. For example, the peptides can be prepared in linear or non-cyclized form using conventional solution or solid phase peptide syntheses and cyclized using standard chemistries. Preferably, the chemistry used to cyclize the peptide will be sufficiently mild so as to avoid substantially degrading the peptide. Suitable procedures for synthesizing the peptides described herein as well as suitable chemistries for cyclizing the peptides are well known in the art.

In various embodiments cyclization can be achieved via direct coupling of the N- and C-terminus to form a peptide (or other) bond, but can also occur via the amino acid side chains. Furthermore it can be based on the use of other functional groups, including but not limited to amino, hydroxy, sulfhydryl, halogen, sulfonyl, carboxy, and thiocarboxy. These groups can be located at the amino acid side chains or be attached to their N- or C-terminus.

Accordingly, it is to be understood that the chemical linkage used to covalently cyclize the peptides of the invention need not be an amide linkage. In many instances it may be desirable to modify the N- and C-termini of the linear or non-cyclized peptide so as to provide, for example, reactive groups that may be cyclized under mild reaction conditions. Such linkages include, by way of example and not limitation amide, ester, thioester, CH₂—NH, etc. Techniques and reagents for synthesizing peptides having modified termini and chemistries suitable for cyclizing such modified peptides are well-known in the art.

Alternatively, in instances where the ends of the peptide are conformationally or otherwise constrained so as to make cyclization difficult, it may be desirable to attach linkers to the N- and/or C-termini to facilitate peptide cyclization. Of course, it will be appreciated that such linkers will bear reactive groups capable of forming covalent bonds with the termini of the peptide. Suitable linkers and chemistries are well-known in the art and include those previously described.

Cyclic peptides and depsipeptides (heterodetic peptides that include ester (depside) bonds as part of their backbone) have been well characterized and show a wide spectrum of biological activity. The reduction in conformational freedom brought about by cyclization often results in higher receptor-binding affinities. Frequently in these cyclic compounds, extra conformational restrictions are also built in, such as the use of D- and N-alkylated-amino acids, α,β-dehydro amino acids or α,α-disubstituted amino acid residues.

Methods of forming disulfide linkages in peptides are well known to those of skill in the art (see, e.g., Eichler and Houghten (1997) Protein Pept. Lett. 4: 157-164).

Reference may also be made to Marlowe (1993) Biorg. Med. Chem. Lett. 3: 437-44 who describes peptide cyclization on TFA resin using trimethylsilyl (TMSE) ester as an orthogonal protecting group; Pallin and Tam (1995) J. Chem. Soc. Chem. Comm. 2021-2022) who describe the cyclization of unprotected peptides in aqueous solution by oxime formation; Algin et al. (1994) Tetrahedron Lett. 35: 9633-9636 who disclose solid-phase synthesis of head-to-tail cyclic peptides via lysine side-chain anchoring; Kates et al. (1993) Tetrahedron Lett. 34: 1549-1552 who describe the production of head-to-tail cyclic peptides by three-dimensional solid phase strategy; Tumelty et al. (1994) J. Chem. Soc. Chem. Comm. 1067-1068, who describe the synthesis of cyclic peptides from an immobilized activated intermediate, where activation of the immobilized peptide is carried out with N-protecting group intact and subsequent removal leading to cyclization; McMurray et al. (1994) Peptide Res. 7: 195-206) who disclose head-to-tail cyclization of peptides attached to insoluble supports by means of the side chains of aspartic and glutamic acid; Hruby et al. (1994) Reactive Polymers 22: 231-241) who teach an alternate method for cyclizing peptides via solid supports; and Schmidt and Langer (1997) J. Peptide Res. 49: 67-73, who disclose a method for synthesizing cyclotetrapeptides and cyclopentapeptides.

These methods of peptide cyclization are illustrative and non-limiting. Using the teaching provide herein, other cyclization methods will be available to one of skill in the art.

H) Identification/Verification of Active Peptides

The active AMPs, STAMPs and the like can be identified and/or validated using an in vitro screening assay. Indeed, in many instances the AMPs and/or STAMPS described herein will be used in vitro as preservatives, topical antimicrobial treatments, and the like. Additionally, despite certain apparent limitations of in vitro susceptibility tests, clinical data indicate that a good correlation exists between minimal inhibitory concentration (MIC) test results and in vivo efficacy of antibiotic compounds (see, e.g., Murray et al. (1994) Antimicrobial Susceptibility Testing, Poupard et al., eds., Plenum Press, New York; Knudsen et al. (1995) Antimicrob. Agents Chemother. 39(6): 1253-1258; and the like). Thus, AMPs useful for treating infections and diseases related thereto are also conveniently identified by demonstrated in vitro antimicrobial activity against specified microbial targets, e.g., as illustrated in Table 4).

Typically, the in vitro antimicrobial activity of antimicrobial agents is tested using standard NCCLS bacterial inhibition assays, or MIC tests (see, National Committee on Clinical Laboratory Standards “Performance Standards for Antimicrobial Susceptibility Testing,” NCCLS Document M100-S5 Vol. 14, No. 16, December 1994; “Methods for dilution antimicrobial susceptibility test for bacteria that grow aerobically-Third Edition,” Approved Standard M7-A3, National Committee for Clinical Standards, Villanova, Pa.).

It will be appreciated that other assays as are well known in the art or that will become apparent to those having skill in the art upon review of this disclosure may also be used to identify active AMPs. Such assays include, for example, the assay described in Lehrer et al. (1988) J. Immunol. Meth., 108: 153 and Steinberg and Lehrer, “Designer Assays for Antimicrobial Peptides: Disputing the ‘One Size Fits All’ Theory,” In: Antibacterial Peptide Protocols, Shafer, Ed., Humana Press, N.J. Generally, active peptides of the invention will exhibit MICs (as measured using the assays described in the examples) of less than about 100 μM, preferably less than about 80 or 60 μM, more preferably about 50 μM or less, about 25 μM or less, or about 15 μM or less, or about 10 μM or less.

IV. Administration and Formulations.

A) Pharmaceutical Formulations.

In certain embodiments, the antimicrobial peptides and/or the chimeric constructs (e.g., targeting moieties attached to antimicrobial peptide(s), targeting moieties attached to detectable label(s), etc.) are administered to a mammal in need thereof, to a cell, to a tissue, to a composition (e.g., a food), etc.). In various embodiments the compositions can be administered to detect and/or locate, and/or quantify the presence of particular microorganisms, microorganism populations, biofilms comprising particular microorganisms, and the like. In various embodiments the compositions can be administered to inhibit particular microorganisms, microorganism populations, biofilms comprising particular microorganisms, and the like.

These active agents (antimicrobial peptides and/or chimeric moieties) can be administered in the “native” form or, if desired, in the form of salts, esters, amides, prodrugs, derivatives, and the like, provided the salt, ester, amide, prodrug or derivative is suitable pharmacologically, i.e., effective in the present method(s). Salts, esters, amides, prodrugs and other derivatives of the active agents can be prepared using standard procedures known to those skilled in the art of synthetic organic chemistry and described, for example, by March (1992) Advanced Organic Chemistry; Reactions, Mechanisms and Structure, 4th Ed. N.Y. Wiley-Interscience.

Methods of formulating such derivatives are known to those of skill in the art. For example, the disulfide salts of a number of delivery agents are described in PCT Publication WO 2000/059863 which is incorporated herein by reference. Similarly, acid salts of therapeutic peptides, peptoids, or other mimetics, and can be prepared from the free base using conventional methodology that typically involves reaction with a suitable acid. Generally, the base form of the drug is dissolved in a polar organic solvent such as methanol or ethanol and the acid is added thereto. The resulting salt either precipitates or can be brought out of solution by addition of a less polar solvent. Suitable acids for preparing acid addition salts include, but are not limited to both organic acids, e.g., acetic acid, propionic acid, glycolic acid, pyruvic acid, oxalic acid, malic acid, malonic acid, succinic acid, maleic acid, fumaric acid, tartaric acid, citric acid, benzoic acid, cinnamic acid, mandelic acid, methanesulfonic acid, ethanesulfonic acid, p-toluenesulfonic acid, salicylic acid, and the like, as well as inorganic acids, e.g., hydrochloric acid, hydrobromic acid, sulfuric acid, nitric acid, phosphoric acid, and the like. An acid addition salt can be reconverted to the free base by treatment with a suitable base. Certain particularly preferred acid addition salts of the active agents herein include halide salts, such as may be prepared using hydrochloric or hydrobromic acids. Conversely, preparation of basic salts of the active agents of this invention are prepared in a similar manner using a pharmaceutically acceptable base such as sodium hydroxide, potassium hydroxide, ammonium hydroxide, calcium hydroxide, trimethylamine, or the like. In certain embodiments basic salts include alkali metal salts, e.g., the sodium salt, and copper salts.

For the preparation of salt forms of basic drugs, the pKa of the counterion is preferably at least about 2 pH lower than the pKa of the drug. Similarly, for the preparation of salt forms of acidic drugs, the pKa of the counterion is preferably at least about 2 pH higher than the pKa of the drug. This permits the counterion to bring the solution's pH to a level lower than the pHmax to reach the salt plateau, at which the solubility of salt prevails over the solubility of free acid or base. The generalized rule of difference in pKa units of the ionizable group in the active pharmaceutical ingredient (API) and in the acid or base is meant to make the proton transfer energetically favorable. When the pKa of the API and counterion are not significantly different, a solid complex may form but may rapidly disproportionate (i.e., break down into the individual entities of drug and counterion) in an aqueous environment.

Preferably, the counterion is a pharmaceutically acceptable counterion. Suitable anionic salt forms include, but are not limited to acetate, benzoate, benzylate, bitartrate, bromide, carbonate, chloride, citrate, edetate, edisylate, estolate, fumarate, gluceptate, gluconate, hydrobromide, hydrochloride, iodide, lactate, lactobionate, malate, maleate, mandelate, mesylate, methyl bromide, methyl sulfate, mucate, napsylate, nitrate, pamoate (embonate), phosphate and diphosphate, salicylate and disalicylate, stearate, succinate, sulfate, tartrate, tosylate, triethiodide, valerate, and the like, while suitable cationic salt forms include, but are not limited to aluminum, benzathine, calcium, ethylene diamine, lysine, magnesium, meglumine, potassium, procaine, sodium, tromethamine, zinc, and the like.

In various embodiments preparation of esters typically involves functionalization of hydroxyl and/or carboxyl groups that are present within the molecular structure of the active agent. In certain embodiments, the esters are typically acyl-substituted derivatives of free alcohol groups, i.e., moieties that are derived from carboxylic acids of the formula RCOOH where R is alky, and preferably is lower alkyl. Esters can be reconverted to the free acids, if desired, by using conventional hydrogenolysis or hydrolysis procedures.

Amides can also be prepared using techniques known to those skilled in the art or described in the pertinent literature. For example, amides may be prepared from esters, using suitable amine reactants, or they may be prepared from an anhydride or an acid chloride by reaction with ammonia or a lower alkyl amine.

In various embodiments, the active agents identified herein are useful for parenteral, topical, oral, nasal (or otherwise inhaled), rectal, or local administration, such as by aerosol or transdermally, for detection and/or quantification, and or localization, and/or prophylactic and/or therapeutic treatment of infection (e.g., microbial infection). The compositions can be administered in a variety of unit dosage forms depending upon the method of administration. Suitable unit dosage forms, include, but are not limited to powders, tablets, pills, capsules, lozenges, suppositories, patches, nasal sprays, injectables, implantable sustained-release formulations, lipid complexes, etc.

The active agents (e.g., antimicrobial peptides and/or chimeric constructs) described herein can also be combined with a pharmaceutically acceptable carrier (excipient) to form a pharmacological composition. In certain embodiments, pharmaceutically acceptable carriers include those approved by a regulatory agency of the Federal or a state government or listed in the U.S. Pharmacopeia or other generally recognized pharmacopeia for use in/on animals, and more particularly in/on humans. A “carrier” refers to, for example, a diluent, adjuvant, excipient, auxiliary agent or vehicle with which an active agent of the present invention is administered.

Pharmaceutically acceptable carriers can contain one or more physiologically acceptable compound(s) that act, for example, to stabilize the composition or to increase or decrease the absorption of the active agent(s). Physiologically acceptable compounds can include, for example, carbohydrates, such as glucose, sucrose, or dextrans, antioxidants, such as ascorbic acid or glutathione, chelating agents, low molecular weight proteins, protection and uptake enhancers such as lipids, compositions that reduce the clearance or hydrolysis of the active agents, or excipients or other stabilizers and/or buffers.

Other physiologically acceptable compounds, particularly of use in the preparation of tablets, capsules, gel caps, and the like include, but are not limited to binders, diluent/fillers, disentegrants, lubricants, suspending agents, and the like.

In certain embodiments, to manufacture an oral dosage form (e.g., a tablet), an excipient (e.g., lactose, sucrose, starch, mannitol, etc.), an optional disintegrator (e.g. calcium carbonate, carboxymethylcellulose calcium, sodium starch glycollate, crospovidone etc.), a binder (e.g. alpha-starch, gum arabic, microcrystalline cellulose, carboxymethylcellulose, polyvinylpyrrolidone, hydroxypropylcellulose, cyclodextrin, etc.), and an optional lubricant (e.g., talc, magnesium stearate, polyethylene glycol 6000, etc.), for instance, are added to the active component or components (e.g., active peptide) and the resulting composition is compressed. Where necessary the compressed product is coated, e.g., known methods for masking the taste or for enteric dissolution or sustained release. Suitable coating materials include, but are not limited to ethyl-cellulose, hydroxymethylcellulose, polyoxyethylene glycol, cellulose acetate phthalate, hydroxypropylmethylcellulose phthalate, and Eudragit (Rohm & Haas, Germany; methacrylic-acrylic copolymer).

Other physiologically acceptable compounds include wetting agents, emulsifying agents, dispersing agents or preservatives that are particularly useful for preventing the growth or action of microorganisms. Various preservatives are well known and include, for example, phenol and ascorbic acid. One skilled in the art would appreciate that the choice of pharmaceutically acceptable carrier(s), including a physiologically acceptable compound depends, for example, on the route of administration of the active agent(s) and on the particular physio-chemical characteristics of the active agent(s).

In certain embodiments the excipients are sterile and generally free of undesirable matter. These compositions can be sterilized by conventional, well-known sterilization techniques. For various oral dosage form excipients such as tablets and capsules sterility is not required. The USP/NF standard is usually sufficient.

In certain therapeutic applications, the compositions of this invention are administered, e.g., topically administered or administered to the oral or nasal cavity, to a patient suffering from infection or at risk for infection or prophylactically to prevent dental caries or other pathologies of the teeth or oral mucosa characterized by microbial infection in an amount sufficient to prevent and/or cure and/or at least partially prevent or arrest the disease and/or its complications. An amount adequate to accomplish this is defined as a “therapeutically effective dose.” Amounts effective for this use will depend upon the severity of the disease and the general state of the patient's health. Single or multiple administrations of the compositions may be administered depending on the dosage and frequency as required and tolerated by the patient. In any event, the composition should provide a sufficient quantity of the active agents of the formulations of this invention to effectively treat (ameliorate one or more symptoms in) the patient.

The concentration of active agent(s) can vary widely, and will be selected primarily based on activity of the active ingredient(s), body weight and the like in accordance with the particular mode of administration selected and the patient's needs. Concentrations, however, will typically be selected to provide dosages ranging from about 0.1 or 1 mg/kg/day to about 50 mg/kg/day and sometimes higher. Typical dosages range from about 3 mg/kg/day to about 3.5 mg/kg/day, preferably from about 3.5 mg/kg/day to about 7.2 mg/kg/day, more preferably from about 7.2 mg/kg/day to about 11.0 mg/kg/day, and most preferably from about 11.0 mg/kg/day to about 15.0 mg/kg/day. In certain preferred embodiments, dosages range from about 10 mg/kg/day to about 50 mg/kg/day. In certain embodiments, dosages range from about 20 mg to about 50 mg given orally twice daily. It will be appreciated that such dosages may be varied to optimize a therapeutic and/or phophylactic regimen in a particular subject or group of subjects.

In certain embodiments, the active agents of this invention are administered to the oral cavity. This is readily accomplished by the use of lozenges, aerosol sprays, mouthwash, coated swabs, and the like.

In certain embodiments, the active agent(s) of this invention are administered topically, e.g., to the skin surface, to a topical lesion or wound, to a surgical site, and the like.

In certain embodiments the active agents of this invention are administered systemically (e.g., orally, or as an injectable) in accordance with standard methods well known to those of skill in the art. In other preferred embodiments, the agents, can also be delivered through the skin using conventional transdermal drug delivery systems, i.e., transdermal “patches” wherein the active agent(s) are typically contained within a laminated structure that serves as a drug delivery device to be affixed to the skin. In such a structure, the drug composition is typically contained in a layer, or “reservoir,” underlying an upper backing layer. It will be appreciated that the term “reservoir” in this context refers to a quantity of “active ingredient(s)” that is ultimately available for delivery to the surface of the skin. Thus, for example, the “reservoir” may include the active ingredient(s) in an adhesive on a backing layer of the patch, or in any of a variety of different matrix formulations known to those of skill in the art. The patch may contain a single reservoir, or it may contain multiple reservoirs.

In one embodiment, the reservoir comprises a polymeric matrix of a pharmaceutically acceptable contact adhesive material that serves to affix the system to the skin during drug delivery. Examples of suitable skin contact adhesive materials include, but are not limited to, polyethylenes, polysiloxanes, polyisobutylenes, polyacrylates, polyurethanes, and the like. Alternatively, the drug-containing reservoir and skin contact adhesive are present as separate and distinct layers, with the adhesive underlying the reservoir which, in this case, may be either a polymeric matrix as described above, or it may be a liquid or hydrogel reservoir, or may take some other form. The backing layer in these laminates, which serves as the upper surface of the device, preferably functions as a primary structural element of the “patch” and provides the device with much of its flexibility. The material selected for the backing layer is preferably substantially impermeable to the active agent(s) and any other materials that are present.

Other formulations for topical delivery include, but are not limited to, ointments, gels, sprays, fluids, and creams. Ointments are semisolid preparations that are typically based on petrolatum or other petroleum derivatives. Creams containing the selected active agent are typically viscous liquid or semisolid emulsions, often either oil-in-water or water-in-oil. Cream bases are typically water-washable, and contain an oil phase, an emulsifier and an aqueous phase. The oil phase, also sometimes called the “internal” phase, is generally comprised of petrolatum and a fatty alcohol such as cetyl or stearyl alcohol; the aqueous phase usually, although not necessarily, exceeds the oil phase in volume, and generally contains a humectant. The emulsifier in a cream formulation is generally a nonionic, anionic, cationic or amphoteric surfactant. The specific ointment or cream base to be used, as will be appreciated by those skilled in the art, is one that will provide for optimum drug delivery. As with other carriers or vehicles, an ointment base should be inert, stable, nonirritating and nonsensitizing.

As indicated above, various buccal, and sublingual formulations are also contemplated.

In certain embodiments, one or more active agents of the present invention can be provided as a “concentrate”, e.g., in a storage container (e.g., in a premeasured volume) ready for dilution, or in a soluble capsule ready for addition to a volume of water, alcohol, hydrogen peroxide, or other diluent.

While the invention is described with respect to use in humans, it is also suitable for animal, e.g., veterinary use. Thus certain preferred organisms include, but are not limited to humans, non-human primates, canines, equines, felines, porcines, ungulates, largomorphs, and the like.

B) Nanoemulsion Formulations.

In certain embodiments the targeting peptides, antimicrobial peptides and/or chimeric moieties (e.g., STAMPs) as described herein are formulated in a nanoemulsion. Nanoemulsions include, but are not limited to oil in water (0/W) nanoemulsions, and water in oil (W/O) nanoemulsions. Nanoemulsions can be defined as emulsions with mean droplet diameters ranging from about 20 to about 1000 nm. Usually, the average droplet size is between about 20 nm or 50 nm and about 500 nm. The terms sub-micron emulsion (SME) and mini-emulsion are used as synonyms.

Illustrative oil in water (0/W) nanoemulsions include, but are not limited to:

Surfactant micelles—micelles composed of small molecules surfactants or detergents (e.g., SDS/PBS/2-propanol) which are suitable for predominantly hydrophobic peptides.

Polymer micelles—micelles composed of polymer, copolymer, or block copolymer surfactants (e.g., Pluronic L64/PBS/2-propanol) which are suitable for predominantly hydrophobic peptides;

Blended micelles: micelles in which there is more than one surfactant component or in which one of the liquid phases (generally an alcohol or fatty acid compound) participates in the formation of the micelle (e.g., Octanoic acid/PBS/EtOH) which are suitable for predominantly hydrophobic peptides;

Integral peptide micelles—blended micelles in which the peptide serves as an auxiliary surfactant, forming an integral part of the micelle (e.g., amphipathic peptide/PBS/mineral oil) which are suitable for amphipathic peptides; and

Pickering (solid phase) emulsions—emulsions in which the peptides are associated with the exterior of a solid nanoparticle (e.g., polystyrene nanoparticles/PBS/no oil phase) which are suitable for amphipathic peptides.

Illustrative water in oil (W/O) nanoemulsions include, but are not limited to:

Surfactant micelles—micelles composed of small molecules surfactants or detergents (e.g., dioctyl sulfosuccinate/PBS/2-propanol, Isopropylmyristate/PBS/2-propanol, etc.) which are suitable for predominantly hydrophilic peptides;

Polymer micelles—micelles composed of polymer, copolymer, or block copolymer surfactants (e.g., PLURONIC® L121/PBS/2-propanol), which are suitable for predominantly hydrophilic peptides;

Blended micelles—micelles in which there is more than one surfactant component or in which one of the liquid phases (generally an alcohol or fatty acid compound) participates in the formation of the micelle (e.g., capric/caprylic diglyceride/PBS/EtOH) which are suitable for predominantly hydrophilic peptides;

Integral peptide micelles—blended micelles in which the peptide serves as an auxiliary surfactant, forming an integral part of the micelle (e.g., amphipathic peptide/PBS/polypropylene glycol) which are suitable for amphipathic peptides; and

Pickering (solid phase) emulsions—emulsions in which the peptides are associated with the exterior of a solid nanoparticle (e.g., chitosan nanoparticles/no aqueous phase/mineral oil) which are suitable for amphipathic peptides.

As indicated above, in certain embodiments the nanoemulsions comprise one or more surfactants or detergents. In some embodiments the surfactant is a non-anionic detergent (e.g., a polysorbate surfactant, a polyoxyethylene ether, etc.). Surfactants that find use in the present invention include, but are not limited to surfactants such as the TWEEN®, TRITON®, and TYLOXAPOL® families of compounds.

In certain embodiments the emulsions further comprise one or more cationic halogen containing compounds, including but not limited to, cetylpyridinium chloride. In still further embodiments, the compositions further comprise one or more compounds that increase the interaction (“interaction enhancers”) of the composition with microorganisms (e.g., chelating agents like ethylenediaminetetraacetic acid, or ethylenebis(oxyethylenenitrilo)tetraacetic acid in a buffer).

In some embodiments, the nanoemulsion further comprises an emulsifying agent to aid in the formation of the emulsion. Emulsifying agents include compounds that aggregate at the oil/water interface to form a kind of continuous membrane that prevents direct contact between two adjacent droplets. Certain embodiments of the present invention feature oil-in-water emulsion compositions that may readily be diluted with water to a desired concentration without impairing their anti-pathogenic properties.

In addition to discrete oil droplets dispersed in an aqueous phase, certain oil-in-water emulsions can also contain other lipid structures, such as small lipid vesicles (e.g., lipid spheres that often consist of several substantially concentric lipid bilayers separated from each other by layers of aqueous phase), micelles (e.g., amphiphilic molecules in small clusters of 50-200 molecules arranged so that the polar head groups face outward toward the aqueous phase and the apolar tails are sequestered inward away from the aqueous phase), or lamellar phases (lipid dispersions in which each particle consists of parallel amphiphilic bilayers separated by thin films of water).

These lipid structures are formed as a result of hydrophobic forces that drive apolar residues (e.g., long hydrocarbon chains) away from water. The above lipid preparations can generally be described as surfactant lipid preparations (SLPs). SLPs are minimally toxic to mucous membranes and are believed to be metabolized within the small intestine (see e.g., Hamouda et al., (1998) J. Infect. Disease 180: 1939).

In certain embodiments the emulsion comprises a discontinuous oil phase distributed in an aqueous phase, a first component comprising an alcohol and/or glycerol, and a second component comprising a surfactant or a halogen-containing compound. The aqueous phase can comprise any type of aqueous phase including, but not limited to, water (e.g., dionized water, distilled water, tap water) and solutions (e.g., phosphate buffered saline solution, or other buffer systems). The oil phase can comprise any type of oil including, but not limited to, plant oils (e.g., soybean oil, avocado oil, flaxseed oil, coconut oil, cottonseed oil, squalene oil, olive oil, canola oil, corn oil, rapeseed oil, safflower oil, and sunflower oil), animal oils (e.g., fish oil), flavor oil, water insoluble vitamins, mineral oil, and motor oil. In certain embodiments, the oil phase comprises 30-90 vol % of the oil-in-water emulsion (i.e., constitutes 30-90% of the total volume of the final emulsion), more preferably 50-80%.

In certain embodiments the alcohol, when present, is ethanol.

While the present invention is not limited by the nature of the surfactant, in some preferred embodiments, the surfactant is a polysorbate surfactant (e.g., TWEEN 20®, TWEEN 40®, TWEEN 60®, and TWEEN 80®), a pheoxypolyethoxyethanol (e.g., TRITON® X-100, X-301, X-165, X-102, and X-200, and TYLOXAPOL®), or sodium dodecyl sulfate, and the like.

In certain embodiments a halogen-containing component is present. the nature of the halogen-containing compound, in some preferred embodiments the halogen-containing compound comprises a chloride salt (e.g., NaCl, KCl, etc.), a cetylpyridinium halide, a cetyltrimethylammonium halide, a cetyldimethylethylammonium halide, a cetyldimethylbenzylammonium halide, a cetyltributylphosphonium halide, dodecyltrimethylammonium halides, tetradecyltrimethylammonium halides, cetylpyridinium chloride, cetyltrimethylammonium chloride, cetylbenzyldimethylammonium chloride, cetylpyridinium bromide, cetyltrimethylammonium bromide, cetyldimethylethylammonium bromide, cetyltributylphosphonium bromide, dodecyltrimethylammonium bromide, tetradecyltrimethylammonium bromide, and the like

In certain embodiments the emulsion comprises a quaternary ammonium compound. Quaternary ammonium compounds include, but are not limited to, N-alkyldimethyl benzyl ammonium saccharinate, 1,3,5-Triazine-1,3,5(2H,4H,6H)-triethanol; 1-Decanaminium, N-decyl-N,N-dimethyl-, chloride (or) Didecyl dimethyl ammonium chloride; 2-(2-(p-(Diisobuyl)cresosxy)ethoxy)ethyl dimethyl benzyl ammonium chloride; 2-(2-(p-(Diisobutyl)phenoxy)ethoxy)ethyl dimethyl benzyl ammonium chloride; alkyl 1 or 3 benzyl-1-(2-hydroxethyl)-2-imidazolinium chloride; alkyl bis(2-hydroxyethyl)benzyl ammonium chloride; alkyl demethyl benzyl ammonium chloride; alkyl dimethyl 3,4-dichlorobenzyl ammonium chloride (100% C12); alkyl dimethyl 3,4-dichlorobenzyl ammonium chloride (50% C14, 40% C12, 10% C16); alkyl dimethyl 3,4-dichlorobenzyl ammonium chloride (55% C14, 23% C12, 20% C16); alkyl dimethyl benzyl ammonium chloride; alkyl dimethyl benzyl ammonium chloride (100% C14); alkyl dimethyl benzyl ammonium chloride (100% C16); alkyl dimethyl benzyl ammonium chloride (41% C14, 28% C12); alkyl dimethyl benzyl ammonium chloride (47% C12, 18% C14); alkyl dimethyl benzyl ammonium chloride (55% C16, 20% C14); alkyl dimethyl benzyl ammonium chloride (58% C14, 28% C16); alkyl dimethyl benzyl ammonium chloride (60% C14, 25% C12); alkyl dimethyl benzyl ammonium chloride (61% C11, 23% C14); alkyl dimethyl benzyl ammonium chloride (61% C12, 23% C14); alkyl dimethyl benzyl ammonium chloride (65% C12, 25% C14); alkyl dimethyl benzyl ammonium chloride (67% C12, 24% C14); alkyl dimethyl benzyl ammonium chloride (67% C12, 25% C14); alkyl dimethyl benzyl ammonium chloride (90% C14, 5% C12); alkyl dimethyl benzyl ammonium chloride (93% C14, 4% C12); alkyl dimethyl benzyl ammonium chloride (95% C16, 5% C18); alkyl dimethyl benzyl ammonium chloride (and) didecyl dimethyl ammonium chloride; alkyl dimethyl benzyl ammonium chloride (as in fatty acids); alkyl dimethyl benzyl ammonium chloride (C12-C16); alkyl dimethyl benzyl ammonium chloride (C12-C18); alkyl dimethyl benzyl and dialkyl dimethyl ammonium chloride; alkyl dimethyl dimethybenzyl ammonium chloride; alkyl dimethyl ethyl ammonium bromide (90% C14, 5% C16, 5% C12); alkyl dimethyl ethyl ammonium bromide (mixed alkyl and alkenyl groups as in the fatty acids of soybean oil); alkyl dimethyl ethylbenzyl ammonium chloride; alkyl dimethyl ethylbenzyl ammonium chloride (60% C14); alkyl dimethyl isoproylbenzyl ammonium chloride (50% C12, 30% C14, 17% C16, 3% C18); alkyl trimethyl ammonium chloride (58% C18, 40% C16, 1% C14, 1% C12); alkyl trimethyl ammonium chloride (90% C18, 10% C16); alkyldimethyl(ethylbenzyl)ammonium chloride (C12-18); Di-(C8-10)-alkyl dimethyl ammonium chlorides; dialkyl dimethyl ammonium chloride; dialkyl dimethyl ammonium chloride; dialkyl dimethyl ammonium chloride; dialkyl methyl benzyl ammonium chloride; didecyl dimethyl ammonium chloride; diisodecyl dimethyl ammonium chloride; dioctyl dimethyl ammonium chloride; dodecyl bis(2-hydroxyethyl)octyl hydrogen ammonium chloride; dodecyl dimethyl benzyl ammonium chloride; dodecylcarbamoyl methyl dimethyl benzyl ammonium chloride; heptadecyl hydroxyethylimidazolinium chloride; hexahydro-1,3,5-thris(2-hydroxyethyl)-s-triazine; myristalkonium chloride (and) Quat RNIUM 14; N,N-Dimethyl-2-hydroxypropylammonium chloride polymer; n-alkyl dimethyl benzyl ammonium chloride; n-alkyl dimethyl ethylbenzyl ammonium chloride; n-tetradecyl dimethyl benzyl ammonium chloride monohydrate; octyl decyl dimethyl ammonium chloride; octyl dodecyl dimethyl ammonium chloride; octyphenoxyethoxyethyl dimethyl benzyl ammonium chloride; oxydiethylenebis (alkyl dimethyl ammonium chloride); quaternary ammonium compounds, dicoco alkyldimethyl, chloride; trimethoxysily propyl dimethyl octadecyl ammonium chloride; trimethoxysilyl quats, trimethyl dodecylbenzyl ammonium chloride; n-dodecyl dimethyl ethylbenzyl ammonium chloride; n-hexadecyl dimethyl benzyl ammonium chloride; n-tetradecyl dimethyl benzyl ammonium chloride; n-tetradecyl dimethyl ethylbenzyl ammonium chloride; and n-octadecyl dimethyl benzyl ammonium chloride.

Nanoemulsion formulations and methods of making such are well known to those of skill in the art and described for example in U.S. Pat. Nos. 7,476,393, 7,468,402, 7,314,624, 6,998,426, 6,902,737, 6,689,371, 6,541,018, 6,464,990, 6,461,625, 6,419,946, 6,413,527, 6,375,960, 6,335,022, 6,274,150, 6,120,778, 6,039,936, 5,925,341, 5,753,241, 5,698,219, and 5,152,923 and in Fanun et al. (2009) Microemulsions: Properties and Applications (Surfactant Science), CRC Press, Boca Ratan Fl.

C) Formulations Optimizing Activity.

In certain embodiments, formulations are selected to optimize binding specificity, and/or binding avidity, and/or antimicrobial activity, and/or stability/conformation of the targeting peptide, antimicrobial peptide, chimeric moiety, and/or STAMP. In this regard, it was a surprising discovery that the activity of certain STAMPs, and presumably the constituent targeting peptides and/or antimicrobial peptides was optimized in the presence of a salt. Accordingly, certain embodiments are contemplated where the targeting peptide and/or antimicrobial peptide, and/or STAMP is formulated in combination with one or more salts. The formulations disclosed herein, however, are not limited to those containing salt(s). Embodiments, are also contemplated where the targeting peptide and/or antimicrobial peptide, and/or STAMP is formulated without the presence of a salt.

In certain embodiments, sodium chloride plus a little potassium chloride resulted in the best activity of the salts tested. However, other salts, e.g., CaCl₂, MgCl₂, MnCl₂ also enhanced activity. Accordingly, in certain embodiments, it is contemplated that the targeting peptide(s), and/or antimicrobial peptide(s), and/or chimeric moieties, and/or STAMPs are formulated with one or more salts.

In certain embodiments suitable salts include any of a number of pharmaceutically acceptable salts. Representative salts include the hydrobromide, hydrochloride, sulfate, bisulfate, phosphate, nitrate, acetate, valerate, oleate, palmitate, stearate, laurate, benzoate, lactate, phosphate, tosylate, citrate, maleate, fumarate, succinate, tartrate, napthylate, mesylate, besylate, glucoheptonate, lactobionate, and laurylsulphonate salts and the like (see, e.g., Berge et al. (1977) J. Pharm. Sci. 66: 1-19), although it is noted that citrate salts appear to inhibit the activity of certain STAMPs.

In certain embodiments pharmaceutically acceptable salts of the present invention include the conventional nontoxic salts or quaternary ammonium salts of the compounds, e.g., from non-toxic organic or inorganic acids. For example, such conventional nontoxic salts include those derived from inorganic acids such as hydrochloride, hydrobromic, sulfuric, sulfamic, phosphoric, nitric, and the like; and the salts prepared from organic acids such as acetic, propionic, succinic, glycolic, stearic, lactic, malic, tartaric, citric, ascorbic, palmitic, maleic, hydroxymaleic, phenylacetic, glutamic, benzoic, salicyclic, sulfanilic, 2-acetoxybenzoic, fumaric, toluenesulfonic, methanesulfonic, benzenesulfonic, ethane disulfonic, oxalic, isothionic, and the like.

In other cases, the compounds of the present invention may contain one or more acidic functional groups and, thus, are capable of forming pharmaceutically-acceptable salts with pharmaceutically-acceptable bases. The term “pharmaceutically-acceptable salts” in these instances refers to the relatively non-toxic, inorganic and organic base addition salts of compounds of the present invention. These salts can likewise be prepared in situ in the administration vehicle or the dosage form manufacturing process, or by separately treating the compound in its free acid form with a suitable base, such as the hydroxide, carbonate or bicarbonate of a pharmaceutically-acceptable metal cation, with ammonia, or with a pharmaceutically-acceptable organic primary, secondary or tertiary amine. Representative alkali or alkaline earth salts include the lithium, sodium, potassium, calcium, magnesium, and aluminum salts and the like. Representative organic amines useful for the formation of base addition salts include ethylamine, diethylamine, ethylenediamine, ethanolamine, diethanolamine, piperazine and the like (see, for example, Berge et al., supra; and Stahl and Wermuth (2002) Handbook of Pharmaceutical Salts: Properties, Selection, and Use, Wiley-VCH, Zurich, Switzerland).

In various embodiments, the salt is simply a sodium chloride and/or a potassium chloride and can readily be prepared, for example, as a phosphate buffered saline (PBS) solution. In certain embodiments, the salt concentration is comparable to that found in 0.5×PBS to about 2.5×PBS, more preferably from about 0.5×PBS to about 1.5×PBS. In certain embodiments optimum activity has been observed in 1×PBS.

In various embodiments, the pH of the formulation ranges from about pH 5.0 to about pH 8.5, preferably from about pH 6.0 to about pH 8.0, more preferably from about pH 7.0 to about pH 8.0. In certain embodiments the pH is about pH 7.4.

While optimum results have been observed for certain STAMPs using a PBS buffer system, other buffer systems are also acceptable. Such buffers include, but are not limited to sulfate buffers, carbonate buffers, Tris buffers, CHAPS buffers, PIPES buffers, and the like, as long as the salt is included.

In various embodiments, the targeting peptide, and/or antimicrobial peptide, and/or chimeric moiety, and/or STAMP is present in the formulation at a concentration ranging from about 1 nM, to about 1, 10, or 100 mM, more preferably from about 1 nM, about 10 nM, about 100 nM, about 1 μM, or about 10 μM to about 50 μM, about 100 μM, about 200 μm, about 300 μM, about 400 μM, or about 500 μM, preferably from about 1 μM, about 10 μM, about 25 μM, or about 50 μM to about 1 mM, about 10 mM, about 20 mM, or about 5 mM, most preferably from about 10 μM, about 20 μM, or about 50 μM to about 100 μM, about 150 μM, or about 200 μM.

D) Home Health Care/Hygiene Product Formulations.

In certain embodiments, one or more of the targeting peptide(s), and/or antimicrobial peptides (AMPs) and/or chimeric moieties, and/or STAMPS described herein are incorporated into healthcare formulations, e.g., for home use. Such formulations include, but are not limited to toothpaste, mouthwash, tooth whitening strips or solutions, contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasal application, wound dressings (e.g., bandages), and the like.

For example, chimeric moieties and/or STAMPs, and/or AMPs directed against S. mutans are well suited for inhibiting frequency or severity of dental caries formation, plaque formation, periodontal disease, and/or halitosis.

Chimeric moieties and/or STAMPs, and/or AMPs directed against Corynebacterium spp, when applied to a skin surface can reduce/eliminate Corynebacterium resulting in a reduction of odors. Such moieties are readily incorporated in soaps, antibiotics, antiseptics, disinfectants, and the like.

The formulation of such health products is well known to those of skill, and the antimicrobial peptides and/or chimeric constructs are simply added to such formulations in an effective dose (e.g., a prophylactic dose to inhibit dental carie formation, etc.).

For example, toothpaste formulations are well known to those of skill in the art. Typically such formulations are mixtures of abrasives and surfactants; anticaries agents, such as fluoride; tartar control ingredients, such as tetrasodium pyrophosphate and methyl vinyl ether/maleic anhydride copolymer; pH buffers; humectants, to prevent dry-out and increase the pleasant mouth feel; and binders, to provide consistency and shape (see, e.g., Table 17). Binders keep the solid phase properly suspended in the liquid phase to prevent separation of the liquid phase out of the toothpaste. They also provide body to the dentifrice, especially after extrusion from the tube onto the toothbrush.

TABLE 17 Typical components of toothpaste. Ingredients Wt % Humectants 40-70 Water  0-50 Buffers/salts/tartar 0.5-10  control Organic thickeners 0.4-2   (gums) Inorganic thickeners  0-12 Abrasives 10-50 Actives (e.g., triclosan) 0.2-1.5 Surfactants 0.5-2   Flavor and sweetener 0.8-1.5 Fluoride sources provide 1000-15000 ppm fluorine.

Table 18 lists typical ingredients used in formulations; the final combination will depend on factors such as ingredient compatibility and cost, local customs, and desired benefits and quality to be delivered in the product. It will be recognized that one or more antimicrobial peptides and/or chimeric constructs described herein can simply be added to such formulations or used in place of one or more of the other ingredients.

TABLE 18 List of typical ingredients. Inorganic Tartar Control Gums Thickeners Abrasives Surfactants Humectants Ingredient Sodium Silica Hydrated Sodium Glycerine Tetrasodium carboxymethyl thickeners silica lauryl sulfate pyrophosphate cellulose Cellulose ethers Sodium Dicalcium Sodium N- Sorbitol Gantrez S-70 aluminum phosphate lauryl silicates digydrate sarcosinate Xanthan Gum Clays Calcium Pluronics Propylene Sodium tri- carbonate glycol polyphosphate Carrageenans Sodium Xylitol bicarbonate Sodium alginate Calcium Sodium Polyethylene pyrophosphate lauryl glycol sulfoacetate Carbopols Alumina

One illustrative formulation described in U.S. Pat. No. 6,113,887 comprises (1) a water-soluble bactericide selected from the group consisting of pyridinium compounds, quaternary ammonium compounds and biguanide compounds in an amount of 0.001% to 5.0% by weight, based on the total weight of the composition; (2) a cationically-modified hydroxyethylcellulose having an average molecular weight of 1,000,000 or higher in the hydroxyethylcellulose portion thereof and having a cationization degree of 0.05 to 0.5 mol/glucose in an amount of 0.5% to 5.0% by weight, based on the total weight of the composition; (3) a surfactant selected from the group consisting of polyoxyethylene polyoxypropylene block copolymers and alkylolamide compounds in an amount of 0.5% to 13% by weight, based on the total weight of the composition; and (4) a polishing agent of the non-silica type in an amount of 5% to 50% by weight, based on the total weight of the composition. In certain embodiments, the antimicrobial peptide(s) and/or chimeric construct(s) described herein can be used in place of the bactericide or in combination with the bactericide.

Similarly, mouthwash formulations are also well known to those of skill in the art. Thus, for example, mouthwashes containing sodium fluoride are disclosed in U.S. Pat. Nos. 2,913,373, 3,975,514, and 4,548,809, and in US Patent Publications US 2003/0124068 A1, US 2007/0154410 A1, and the like. Mouthwashes containing various alkali metal compounds are also known: sodium benzoate (WO 9409752); alkali metal hypohalite (US 20020114851A1); chlorine dioxide (CN 1222345); alkali metal phosphate (US 2001/0002252 A1, US 2003/0007937 A1); hydrogen sulfate/carbonate (JP 8113519); cetylpyridium chloride (CPC) (see, e.g., U.S. Pat. No. 6,117,417, U.S. Pat. No. 5,948,390, and JP 2004051511). Mouthwashes containing higher alcohol (see, e.g., US 2002/0064505 A1, US 2003/0175216 A1); hydrogen peroxide (see, e.g., CN 1385145); CO₂ gas bubbles (see, e.g., JP 1275521 and JP 2157215) are also known. In certain embodiments, these and other mouthwash formulations can further comprise one or more of the AMPs or compound AMPs of this invention.

Contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, and aerosolizers for oral and/or nasal application, and the like are also well known to those of skill in the art and can readily be adapted to incorporate one or more antimicrobial peptide(s) and/or chimeric construct(s) described herein.

The foregoing pharmaceutical and/or home healthcare formulations and/or devices are meant to be illustrative and not limiting. Using teaching provided herein, the antimicrobial peptide(s) and/or chimeric construct(s) described herein can readily be incorporated into other products.

E) Illustrative Oral Care Formulations.

The targeting peptide(s), and/or antimicrobial peptide(s), and/or chimeric moieties, and/or STAMPs described herein can be used for a number of applications, e.g., as described above. In certain embodiments anti-S. mutans STAMPs, AMPs, and/or other chimeric moieties can be used to reduce the incidence or severity of dental caries, inhibit plaque formation, reduce halitosis, and the like. Accordingly, in certain embodiments, such moieties are included in devices and formulations for dental applications e.g., tea or other drinks, toothpick coatings, dental floss coatings, toothpaste, gel, mouthwash, varnish, even professional dental products.

In certain embodiments, methods of treating or reducing the incidence, duration, or severity of periodontal disease are provided. The methods can include applying to the gingival crevice or periodontal pocket a composition comprising a targeting peptide, and/or antimicrobial peptide, and/or STAMP, and/or other chimeric moiety as described herein with a carrier/stabilizing agent. In the composition applied, the carrier/stabilizing agent can provide retention, tissue penetration, deposition and sustained release of the active agent (e.g., STAMP) for reducing the population of specific bacterial species within a periodontal biofilm and associated tissues. In certain embodiments, the carrier agent provides penetration and retention into the gingival crevice or periodontal pocket and associated tissues with sustained release of the active agent to enhance the reduction in population of select bacteria within the gingival tissue and dentinal tubule tissue.

In various embodiments, carrier agents can include, but are not limited to polylactide, polyglycolide, polylactide-co-glycolide, polycaprolactone, cellulosic-based polymers, ethylene glycol polymers and its copolymers, oxyethylene polymers, polyvinyl alcohol, chitosan and hyaluronan and its copolymers. In an aspect, the carrier agents include hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxypropylmethyl cellulose, hydroxymethyl cellulose, polyvinyl alcohol, polyethylene glycol, polyethylene oxide, ethylene oxide-propylene oxide co-polymers, chitosan, hyaluronan and its copolymers, or combinations thereof. In another aspect, the carrier agents include hyaluronan or hyaluronic acid and copolymers including salts of hyaluronic acid, esters of hyaluronic acid, cross-linked gels of hyaluronic acid, enzymatic derivatives of hyaluronic acid, chemically modified derivatives of hyaluronic acid or combinations thereof. As used herein, hyaluronic acid broadly refers to naturally occurring, microbial and synthetic derivatives of acidic polysaccharides of various molecular weights constituted by residues of D-glucuronic acid polysaccharides and N-acetyl-D-glucosamine.

In certain embodiments, the active agent (e.g., STAMP, AMP, etc.) and the carrier agent are in the form of an admixture, in the form of a complex, covalently coupled, or a combination thereof. In certain embodiments, the carrier agent comprises a bioadhesive. Suitable bioadhesive carrier agents include, but are not limited to a cellulose based polymer and/or a dextrin. Suitable cellulose based polymers include, but are not limited to hydroxyethyl cellulose, hydroxypropyl cellulose, hydroxymethyl cellulose, or a mixture thereof. In one illustrative embodiment, the bioadhesive carrier agent includes polylactide, polyglycolide, polylactide-co-glycolide, polyethylene glycol, hyaluronan, hyaluronic acid, chitosan, or a mixture thereof. In certain embodiments the bioadhesive carrier agent can include a copolymer comprising polyethylene glycol, hyaluronan, hyaluronic acid, chitosan, or a mixture thereof.

In certain embodiments, the carrier agent penetrates periodontal tissues. Suitable penetrating carrier agents include, but are not limited to hyaluronic acid, a hyaluronic acid derivative, chitosan, a chitosan derivative, or a mixture thereof. In an embodiment, the penetrating carrier agent includes a salt of hyaluronic acid, an ester of hyaluronic acid, an enzymatic derivative of hyaluronic acid, a cross-linked gel of hyaluronic acid, a chemically modified derivative of hyaluronic acid, or a mixture thereof.

V. Microorganism Detection.

As indicated above, the targeting moieties and/or STAMPs are useful in diagnostic compositions and methods to determine the presence or absence and/or to quantify the amount of one or microorganisms present in the environment, in a food stuff, in a biological sample, and the like.

For example, targeting peptide-antimicrobial peptide conjugates (e.g. Specifically targeted antimicrobial peptides (STAMPs)) can be used as diagnostic reagents. STAMPs (and other targeted antimicrobial constructs described herein) have the ability to specifically bind to microorganisms, for example, S. mutans, and permeabilize or disrupt their membrane such that cell impermeable dyes or other reagent (propidium iodide, etc.) may enter the microorganism or intracellular molecules or contents (ATP, DNA, Calcium, etc.) of the targeted microorganism are caused to be released into the environment for analysis. In one method a STAMP, for example, C16G2, can permeabilize or disrupt the membrane of target microorganisms, for example, S. mutans, in a prepared culture or clinical sample by itself, in a biofilm in vitro or in vivo. To the sample a cell impermeable dye (e.g. propidium iodide, etc.) is added to label and allow for detection of those microorganisms targeted by the STAMP. Cell permeable dyes (e.g. SYTO9) can also be added to label and detect the entire population of microorganisms in the sample. Labeled cells can then be quantified by fluorescence microscopy, fluorometry, flow cytometry or other method.

In another example, a STAMP treated sample is mixed with luciferase and luciferin which reacts with the ATP released from the STAMP treated cells and the resulting luminescence is used to detected and quantify targeted cells.

VI. Kits.

In another embodiment this invention provides kits for the inhibition of an infection and/or for the treatment and/or prevention of dental caries in a mammal. The kits typically comprise a container containing one or more of the active agents (i.e., the antimicrobial peptide(s) and/or chimeric construct(s)) described herein. In certain embodiments the active agent(s) can be provided in a unit dosage formulation (e.g., suppository, tablet, caplet, patch, etc.) and/or may be optionally combined with one or more pharmaceutically acceptable excipients.

In certain embodiments the kits comprise one or more of the home healthcare product formulations described herein (e.g., toothpaste, mouthwash, tooth whitening strips or solutions, contact lens storage, wetting, or cleaning solutions, dental floss, toothpicks, toothbrush bristles, oral sprays, oral lozenges, nasal sprays, aerosolizers for oral and/or nasal application, and the like).

In certain embodiments kits are provided for detecting and/or locating and/or quantifying certain target microorganisms and/or cells or tissues comprising certain target microorganisms, and/or prosthesis bearing certain target microorganisms, and/or biofilms comprising certain target microorganisms. In various embodiments these kits typically comprise a chimeric moiety comprising a targeting moiety and a detectable label as described herein and/or a targeting moiety attached to an affinity tag for use in a pretargeting strategy as described herein.

In addition, the kits optionally include labeling and/or instructional materials providing directions (i.e., protocols) for the practice of the methods or use of the “therapeutics” or “prophylactics” or detection reagents of this invention. Certain instructional materials describe the use of one or more active agent(s) of this invention to therapeutically or prophylactically to inhibit or prevent infection and/or to inhibit the formation of dental caries. The instructional materials may also, optionally, teach preferred dosages/therapeutic regiment, counter indications and the like.

While the instructional materials typically comprise written or printed materials they are not limited to such. Any medium capable of storing such instructions and communicating them to an end user is contemplated by this invention. Such media include, but are not limited to electronic storage media (e.g., magnetic discs, tapes, cartridges, chips), optical media (e.g., CD ROM), and the like. Such media may include addresses to internet sites that provide such instructional materials.

EXAMPLES

The following examples are offered to illustrate, but not to limit the claimed invention.

Example 1 Design and Activity of a “Dual-Targeted” Antimicrobial Peptide

Numerous reports have indicated the important role of human normal flora in the prevention of microbial pathogenesis and disease. Evidence suggests that infections at mucosal surfaces result from the outgrowth of subpopulations or clusters within a microbial community, and are not linked to one pathogenic organism alone. In order to preserve the protective normal flora while treating the majority of infective bacteria in the community, a tunable therapeutic is necessary that can discriminate between benign bystanders and multiple pathogenic organisms. Here we describe the proof-of-principle for such a multi-targeted antimicrobial: a multiple-headed specifically-targeted antimicrobial peptide (MH-STAMP). The completed MH-STAMP, M8(KH)-20, displays specific activity against targeted organisms in vitro (Pseudomonas aeruginosa and Streptococcus mutans) and can remove both species from a mixed planktonic culture with little impact against untargeted bacteria. These results demonstrate that a functional, dual-targeted molecule can be constructed from wide-spectrum antimicrobial peptide precursor.

Introduction

For nearly 30 years antimicrobial peptides (AMPs) have been rigorously investigated as alternatives to small molecule antibiotics and potential solutions to the growing crisis of antibiotic resistant bacterial infections (Ganz (2003) Nat Rev Immunol., 3: 710-720; Hancock and Lehrer (1998)., 16: 82-88). Numerous reports have characterized potential AMPs from natural sources, and a great body of work has been carried out designing “tailor-made” AMPs due to the approachable nature of solid-phase peptide synthesis (SPPS) (Genco et al. (2003) Int J Antimicrob Agents, 21: 75-78; He and Eckert (2007) Antimicrob Agents Chemother., 51: 1351-1358). Several examples of the latter have shown remarkable activities in vitro against fungi, Gram-positive and Gram-negative bacteria, as well as some enveloped viruses (Brogden (2005) Nat Rev Microbiol. 3: 238-250).

Unlike small molecule antibiotics that may lose activity when their basic structures are modified even incrementally, peptides are a convenient canvas for molecular alteration. AMPs can be optimized through the incorporation of more or less hydrophobic or charged amino acids, which has been shown to affect selectivity for Gram-positive, Gram-negative or fungal membranes (Muhle and Tam J P (2001) Biochemistry, 40: 5777-5785; Tossi et al. (2000) Biopolymers 55: 4-30). Additionally, lysine residues can be utilized to improve AMP activity per μM. In this approach, multiple AMP chains can be attached to a single peptide scaffold through branching from lysine epsilon-amines (Tam et al. (2992) Eur. J. Biochem., 269: 923-932; Pini et al. (2005) Antimicrob Agents Chemother., 2005; 49: 2665-2672). AMP activity can be specifically tuned through the attachment of a targeting peptide region, as described for a novel class of molecules, the specifically-targeted antimicrobial peptides, or STAMPs (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3651-3657; Eckert et al. (2006) Antimicrob Agents Chemother., 50: 1480-1488). These chimeric molecules can consist of functionally independent targeting and killing moieties within a linear peptide sequence. A pathogenic bacterium recognized (i.e. bound) by the targeting peptide can be eliminated from a multi-species community with little impact to bystander normal flora. As an extension of this concept, we hypothesized that a STAMP could be constructed with multiple targeting peptide “heads” attached to a single AMP by utilizing a central lysine residue branch point. Potentially, targeting “heads” could be specific for the same pathogen, or have different binding profiles. Utilizing the former approach, microbial resistance evolution linked to a targeting peptide could be inhibited or reduced, as no single microbial population would have the genetic diversity necessary to mutate multiple discrete targeting peptide receptors in one cell (Drake et al. (1998) Genetics 148: 1667-1686).

Multi-headed STAMP (MH-STAMP) molecules with differing bacterial targets may have appeal in treating poly-microbial infections, or where it may be advantageous to remove a cluster of biofilm constituents without utilizing several distinct molecules; for example in the simultaneously treatment of dental caries and periodontitis, or in the eradication of the Propionibacteria spp. and Staphylococcus spp. involved in acne and skin infections, respectively.

In this example, we present the proof-of-principle design, synthesis and in vitro activity of such a MH-STAMP, M8(KH)-20. Previously, we identified two functional STAMP targeting domains, one with specific recognition of the cariogenic pathogen S. mutans (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3651-3657), and the other with Pseudomonas spp.-level selectivity (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3833-3838). Conjoined to a normally wide-spectrum linear AMP, we observed antimicrobial effects directed specifically to P. aeruginosa and S. mutans in vitro. Additionally, treatment of mixed bacterial communities with the multi-headed MH-STAMP resulted in the specific eradication of the target organisms with little impact on bystander population levels.

Materials and Methods

Bacterial Strains and Growth Conditions

P. aeruginosa ATCC 15692, Klebsiella pneumoniae KAY 2026 (Sprenger and Lengeler (1984) J Bacteriol., 157: 39-45), Escherichia coli DH5α (pFW5, spectinomycin resistance) (Podbielski et al. (1996) Gene, 177: 137-147), Staphylococcus aureus Newmann (Duthie and Lorenz (1952) J Gen Microbiol., 6: 95-107), and Staphylococcus epidermidis ATCC 35984 were cultivated under aerobic conditions at 37° C. with vigorous shaking Aerobic Gram-negative organisms were grown in Lauri-Bertaini (LB) broth and Gram-positive bacteria in Brain-heart infusion (BHI) broth. Streptococcus mutans JM11 (spectinomycin resistant, UA140 background) was grown in Todd-Hewitt (TH) broth under anaerobic conditions (80% N2, 15% CO₂, 5% H2) at 37° C. Merritt et al. (2005) J Microbiol Meth., 61: 161-170. All bacteria were grown overnight to an OD600 of 0.8-1.0 prior to appropriate dilution and antimicrobial testing.

Synthesis of Multi-Head STAMP Peptides

Conventional solid-phase peptide synthesis (SPPS) methodologies were utilized for the construction of all peptides shown in FIG. 15 (Symphony Synthesizer, PTI, Tucson, Ariz.). Chemicals, amino acids, and synthesis resins were purchased from Anaspec (San Jose, Calif.). BD2.20 (FIRKFLKKWLL (SEQ ID NO:3226), amidated c-terminus, mw 1491.92), an antimicrobial peptide developed in our laboratory with robust antimicrobial activity against a number of bacterial species (Table 19), served as the root sequence to which differing targeting peptides were attached: Firstly, BD2.20 was synthesized by SPPS (Rink-Amide-MBHA resin, 0.015 mmol), followed by the stepwise coupling of a functionalized alkane (NH₂(CH₂)₇COOH), and an Fmoc-protected Lys (side-chain protected with 4-methyltrityl (Mtt)) to the N-terminus. Standard SPPS methods were then employed for the step-wise addition of the S. mutans targeting peptide M8 plus a tri-Gly linker region (TFFRFLNR-GGG (SEQ ID NO:3227)) to the N-terminal of the central Lys. After assembly of Fmoc-M8-GGG-K(Mtt)-(CH₂)₇C0-BD2.20 (SEQ ID NO:3228), the Fmoc group was removed with 25% piperidine in DMF and the N-terminal was re-protected with an acetyl group with Ac₂O/DIEA (1:1, 20 molar excess) for 2 hours. The Mtt-protected amino group of the central Lys was then selectively exposed with 2% TFA in DCM (1.5 mL) for 15 minutes (three cycles of 5 min). The resulting product was reloaded into the synthesizer and the peptide sequence built from the Lys side-chain was completed with standard Fmoc SPPS methods. As shown in FIG. 15, the completed MH-STAMP M8(KH)-20 contained the side-chain peptide KH (Pseudomonas spp.-targeting, KKHRKHRKHRKH-GGG (SEQ ID NO:3229)), while in MH-STAMP M8(BL)-20 a peptide with no bacterial binding (data not shown), BL-1 (DAANEA-GGG), was utilized. BL(KH)-20 was constructed identically to M8(KH)-20, utilizing BL-1 in place of M8 (FIG. 15).

TABLE 19 MICs of MH-STAMPs and component peptides. MIC (μM) P. aeruginosa E. coli K. pneumoniae S. mutans S. epidermidis S. aureus BD2.20 14.4 ± 4.40 5.47 ± 1.41 2.98 ± 0.47 2.86 ± 0.60 5.11 ± 1.58 5.625 ± 1.29 M8(KH)- 11.95 ± 3.32  2.72 ± 0.59 3.13 6.25 3.13  5.64 ± 1.07 20 M8(BL)- 50 5.97 ± 0.94 6.88 ± 1.98 6.25 6.25 18.05 ± 6.58 20 BL(KH)- 27.5 ± 7.90 6.25 6.25 6.25 6.25 6.25 20 Average MIC with standard deviation, n = 10 assays.

Synthesis progression was monitored by the ninhydrin test, and completed peptides cleaved from the resin with 95% TFA utilizing appropriate scavengers, and precipitated in methyl tert-butyl ether. Purification and MH-STAMP quality was confirmed by HPLC (Waters, Milford, Mass.) using a linear gradient of increasing mobile phase (acetonitrile 10 to 90% in water with 0.1% TFA) and a Waters XBridge BEH 130 C18 column (4.6×100 mm, particle size 5 μm). Absorbance at 215 nm was utilized as the monitoring wavelength, though 260 and 280 nm were also collected. LC spectra were analyzed with MassLynx Software v.4.1 (Waters). Matrix-assisted laser desorption ionization (MALDI) mass spectroscopy was utilized to confirm correct peptide mass (Voyager System 4291, Applied Biosystems) (Anderson et al. (2008) Biotechnol Lett., 30: 813-818).

MIC Assay

Peptides were evaluated for basic antimicrobial activity by broth microdilution, as described previously (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3651-3657; Eckert et al. (2006) Antimicrob Agents Chemother., 50: 1480-1488). Briefly, ˜1×105 cfu/mL bacteria were diluted in TH (S. mutans), or Mueller-Hinton (MH) broth (all other organisms) and distributed to 96-well plates. Serially-diluted (2-fold) peptides were then added and the plates incubated at 37° C. for 18-24 h. Peptide MIC was determined as the concentration of peptide that completely inhibited organism growth when examined by eye (clear well). All experiments were conducted 10 times.

Post-Antibiotic Effect Assay

The activity and selectivity of MH-STAMPs after a 10 min incubation was determined by growth retardation experiments against targeted and untargeted bacteria in monocultures, as described previously (Id.). Cells from overnight cultures were diluted to ˜5×106 cfu/mL in MH (or TH with 1% sucrose for S. mutans), normalized by OD600 0.05-0.1 and seeded to 96-well plates. Cultures were then grown under the appropriate conditions for 2 h (3 h for S. mutans) prior to the addition of peptides for 10 min. Plates were then centrifuged at 3000×g for 5 min, the supernatants discarded, fresh medium returned (MH or TH without sucrose for S. mutans), and incubation resumed. Bacterial growth after treatment was then monitored over time by OD600.

Microbial Population Shift Assay

Mixed planktonic populations of P. aeruginosa, E. coli, S. epidermidis, and S. mutans were utilized to examine the potential of MH-STAMPs to direct species composition within a culture after treatment. Samples were prepared containing: ˜6×10⁴ cfu/mL S. mutans, ˜2×10⁴ cfu/mL E. coli, ˜2×10⁴ cfu/mL S. epidermidis, and ˜0.5×10⁴ cfu/mL P. aeruginosa in BHI (mixed immediately before peptide addition). Peptide (10 μM) or mock-treatment (1×PBS) was then added and samples were incubated at 37° C. for 24 h under anaerobic conditions (80% N₂, 15% CO₂, 5% H₂). After incubation, samples were serially diluted (1:10) in 1×PBS and aliquots from each dilution were then spotted to agar plates selective for each species in the mixture: TH plus 800 μg/mL spectinomycin (S. mutans), LB plus 25 μg/mL ampicillin (P. aeruginosa), LB plus 200 μg/mL spectinomycin (E. coli), and mannitol salt agar (MSA, S. epidermidis) in order to quantitate survivors from each species. Plates were then incubated 37° C. under aerobic conditions (TH plates were incubated anaerobically) and colonies counted after 24 h to determine survivors. Expected colony morphologies were observed for each species when plated on selective media. Gram stains and direct microscopic observation (from select isolated colonies) were undertaken to confirm species identity (data not shown). The detection limit of the assay was 200 cfu/mL.

Results

Design and Synthesis of Multi-Headed STAMPs

We constructed a prototype MH-STAMP from the well-established targeting peptides KH (specific to Pseudomonas spp) and M8 (specific for Streptococcus mutans). The wide-spectrum antimicrobial peptide BD2.20 was utilized as the base AMP for all MH171 STAMP construction. BD2.20 is a novel synthetic AMP with a cationic and amphipathic residue arrangement, which has robust MICs against a variety of Gram-negative and Gram-positive organisms (Table 19). For the synthesis of MH-STMAP M8(KH)-20 (construct presented in FIG. 15), BD2.20 and a Lys (Mtt-protected side-chain) residue were joined via an activated alkane spacer, followed by addition of the M8 targeting peptide to the N-terminus of the product. Selective deprotection of the central Lys(Mtt) side chain was then undertaken and the KH targeting peptide attached. The correct molecular mass (4888.79) and ˜90% purity was confirmed by HPLC and MALDI mass spectrometry (FIG. 16).

The non-binding “blank” targeting peptide BL-1 was incorporated into the synthesis scheme in place of KH or M8 to construct variant MH-STAMPs possessing a single functional targeting head: M8(BL)-20 and BL(KH)-20. The correct MW and acceptable purity were observed for these MH-STAMPs (FIG. 15, data not shown).

General Antimicrobial Activity of Multi-Head Constructs

After synthesis, the completed MH-STAMPs were evaluated for general antimicrobial activity by MIC against a panel of bacteria. As shown in Table 19, the MH-STAMP constructs M8(KH)-20, BL(KH)-20, and M8(BL)-20 were found to have similar activity profiles to that of BD2.20 for the organisms examined (less than two titration steps in 10-fold difference). Additionally, we observed a difference in general susceptibility between P. aeruginosa and the other organisms tested, suggesting this bacterium is more resistant to BD2.20. Overall, these data indicate that the addition of the targeting domains to the base sequence was tolerated and did not completely inhibit the activity of the antimicrobial peptide.

Peptide selectivity could not be determined utilizing these methods, as STAMPs and their parent AMP molecules often display similar MICs, but have radically different antimicrobial kinetics and selectivity due to increased specific-killing mediated by the targeting regions (Id.). Therefore, we performed different experiments to test for antimicrobial selectivity and functional MH-STAMP construction.

Selectivity and Post-Antibiotic Effect of MH-STAMP Constructs

MH-STAMP antimicrobial kinetics was ascertained utilizing a variation of the classical post-antibiotic effect assay, which measures the ability of an agent to affect an organism's growth after a short exposure period. Monocultures of MH-STAMP-targeted and untargeted organisms were exposed to M8(KH)-20, M8(BL)-20, BL(KH)-20, or unmodified BD2.20, then allowed to recover. As shown in FIG. 17A, S. mutans growth was effectively retarded by M8-containing constructs (M8(KH)-20, M8(BL)-20), but was not altered by a MH-STAMP construct lacking this region (BL(KH)-20). Similarly, the growth of the other targeted bacterium, P. aeruginosa, was inhibited in a KH-dependant manner (FIG. 17B). In comparison, the non-targeted bacteria E. coli, S. aureus, and S. epidermidis were not inhibited by treatment with any MH-STAMP and were only inhibited by the base antimicrobial peptide BD2.20, which displayed robust antimicrobial activity against all examined strains. These results indicate that MH-STAMPs containing KH or M8 targeting domains have activity against P. aeruginosa or S. mutans, respectively, and not other bacteria. Furthermore, replacement of the targeting region with a non-binding peptide abolishes specific activity.

Ability of MH-STAMPs to Direct a “Population Shift” within a Mixed Species Population

We hypothesized that potential MH-STAMP dual-functionality could affect a particular set of bacteria within a mixed population, thereby promoting the outgrowth of non-targeted organisms and “shifting” the constituent makeup. To examine this possibility, defined mixed populations of planktonic cells were treated continuously and the make-up of the community examined after 24 h. As shown in FIG. 18, treatment with the wide spectrum AMP BD2.20 resulted in a significant loss of recoverable cfu/mL after 24 h from all species in the mixture. Treatment with M8(KH)-20 was found to alter this pattern; we observed ˜1×10⁵ cfu/mL surviving E. coli and S. epidermidis, but did not recover S. mutans or P. aeruginosa cfu/mL. In BL(KH)-20 treated samples, P. aeruginosa cfu/mL were not observed, though we recovered higher than input cfu/mL from S. mutans and unchanged numbers of S. epidermidis and E. coli. In samples exposed to M8(BL)-20, S. mutans recoverable cfu/mL were greatly reduced compared to input cfu/mL, while other species were not affected or affected to a lesser extent. Interestingly, these results suggest that M8(KH)-20, M8(BL)-20, and BL(KH)-20 retain their ability to affect organisms recognized by the targeting regions present, even within a mixed population of bacteria.

Discussion

Our results indicate that we have successfully constructed a STAMP with dual antimicrobial specificities controlled by the targeting peptides present in the molecule; KH for Pseudomonas spp, M8 for S. mutans. In a closed multi-species system (FIG. 18), the dual specificity of M8(KH)-20 was readily discernable: the population of the culture “shifted” away from targeted organisms after MH-STAMP treatment. The targeted bacteria were eliminated and the population of untargeted organisms increased, to varying degrees, above-input cfu/mL. Additionally, interruption of KH or M8 in the MH-STAMP construct with the non-binding peptide BL-1 resulted in the expected elimination of only one targeted species. These results support the hypothesis that functional MH-STAMPs could be constructed from a wide-spectrum AMP base.

The emergence of metagenomics and the development of more sensitive molecular diagnostics has driven an increase in the understanding of human-associated microbial ecologies and host-microbe interactions (Aas et al. (2005) J Clin Microbiol., 43: 5721-5732; Boman (2000) Immunol Rev., 173: 5-16; Kreth et al. (2005) J Bacteria, 187: 7193-7203). At mucosal surfaces, it has become clear that our bodies harbor an abundance of residential flora which may impact innate and humoral immunity, nutrient availability, protection against pathogens, and even host physiology (Metges (2000) J Nutr., 130: 1857S-64; Sears (2005) Anaerobe, 11: 247-251; Lievin-Le et al. (2006) Clin Microbiol Rev., 19: 315-337; DiBaise et al. (2008) Mayo Clinic Proceedings 83: 460-469). Furthermore, findings have indicated that shifts in the diversity of normal flora are associated with negative clinical consequences; for example the overgrowth of S. mutans in the oral cavity during cariogenesis (linked to the uptake of sucrose) or the antibiotic-assisted colonization of the intestine by Clostridium difficle (Loesche (1986) Microbiol Rev., 50: 353-380; Gould and McDonald (2998) Crit Care 12: 203). Other population shifts may be linked to axilla odor (Corynebacteria spp) (Leyden et al. (1981) J Invest Dermatol., 77: 413-416; Elsner (2006) Curr Probl Dermatol., 33: 35-41), or even host obesity. Given the quantity and diversity of microbes present, pathogenesis at mucosal surfaces is not likely to be associated with the overgrowth of a single strain or species. More often, it is a population shift resulting in the predominance of two or more species; for example the persistence of Burkholderia cepacia and P. aeruginosa in cystic fibrosis airway or Treponema denticola and Porphymonas gingivalis and other “red cluster” organisms in gingivitis (Govan and Deretic (1996) Microbiol Rev., 60: 539-574; Paster et al. (2001) J Bacteriol., 183: 3770-3783). In many cases (such as the latter) these species may have only distant phylogenetic relationships and display differential susceptibilities to antibiotic therapies resulting in persistent disease progression despite treatment (Schlessinger (1988) Clin Microbiol Rev., 1: 54-59; Tresse et al. (1997) J Antimicrob Chemother., 40: 419-421). Currently, available treatments for infections of mucosal surfaces are largely non-specific (traditional small-molecule antibiotics, mechanical removal), and thus are not effective in retaining flora or shifting the constituent balance back to a health-associated composition (Keene and Shklair (1974) J Dent Res., 53: 1295). There is a need for a therapeutic treatment that can selectively target multiple pathogens, regardless of their phylogenetic relationship, and MH-STAMPs can help achieve this goal.

In monoculture experiments (FIG. 17), our results suggest that M8 or KH inclusion in the MH-STAMP drove activity towards S. mutans or P. aeruginosa, but also that the presence of a targeting domain reduced the activity of the parent AMP BD2.20 against untargeted organisms. In contrast, the results of our MIC assays (Table 19) indicate little difference in activity between BD2.20 and any MH-STAMP. Against untargeted organisms, the M8 and KH regions are likely to have a negative, but not completely inhibitory, impact on BD2.20 activity. Given the long duration of activity and the lower inoculum size in the MIC assay (compared with experiments in FIG. 17), it is likely that all BD2.20-containing peptides could reach equal levels of growth inhibition, despite large and target-specific differences in antimicrobial speed. This pattern of results was also observed when comparing MICs of targeted and untargeted organisms utilizing STAMPs against S. mutans and Pseudomonas mendocina (Eckert et al. (2006) Antimicrob Agents Chemother., 50: 3651-3657; Eckert et al. (2006) Antimicrob Agents Chemother., 50: 1480-1488).

Although more rigorous studies and a more medically relevant combination of pathogen targets is desirable, these findings indicate that it is possible to design an antimicrobial peptide-based therapeutic with multiple and defined fidelities in vitro. MH-STAMPs may help improve human health through the promotion of healthy microbial constituencies.

Example 2 Synthesis of Peptide Porphyrin Conjugate

The mixture of coupling reagent HATU (5 eq. excess, 10 mg) and purpurin-18 (MW 564, 5 eq excess, 15 mg) in 600 mL dry dichloromethane (DCM):DMF:dimethylsulphoxide (DMSO) (1:1:1 (v/v)) was added to the peptide resin (1 molar equivalent, 15 mg) which was swelled by placing in minimal DMF for 30 min prior to reaction. 26 μL (10 molar equivalents) DIPEA was then added to the reaction flask to initiate the reaction. The reaction mixture was protected with argon and stirred at room temperature for 3 h.

After finishing, the reaction mixture was then passed down a sintered glass filtered vial and extensively washed with DMF and DCM to remove all waste reagents. The resin was then dried overnight in vacuum, and cleaved with 1 ml of trifluoroacetic acid (TFA)/thioanisole/water/EDT (10/0.5/0.5/025) for 2 hr at room temperature, and the cleavage solution was precipitated with 10 mL methyl-tert butyl ether. The precipitate was washed twice with the same amount of ether.

Example 3 Synthesis of Peptide CSA Conjugate

To the fully protected peptide (solution of B43-GGG (FIDSFIRSF-GGG, 0.025 mmol) and tri-Boc-CSA-15 (0.0125 mol) in 300 μL DMF, DCC (7.7 mg), HOBt (5.1 mg) and 13 μL DIEA were added in iced-bath. After stirred at room temperature for four days, the reaction mixture was poured into 5 ml water and extracted with chloroform (5×3 mL). The CHCl₃ extract was evaporated under vacuum and dried in a lyophilizer overnight. The dried CHCl₃ extracts was then dissolved in 1 mL DCM followed by added 1 mL of TFA in iced-bath. The reaction mixture was further stirred at room temperature for 2 hours and precipitated with methyl tert-butyl ether (10 mL). The precipitate was further washed once with the same amount ether and dried in vacuum.

Example 4 STAMPs Against Corynebacterium jeikeium and Streptococcus mutans

This example illustrates the development of STAMPs to selectively target and reduce or eliminate Streptococcus mutans (dental caries) or Corynebacterium jeikeium (body odor, opportunistic infections) from mixed microbial populations.

Axilla odor is caused by overgrowth of, and metabolite production from, Corynebacterium spp, which replaces Staphylococcus and Micrococcus spp associated with less odor. Current hygiene (soaps, antibiotics, antiseptics, disinfectants) practices remove all bacteria, allowing the ratio of Corynebacteria to normal flora to remain high during regrowth. Deodorants and anti-perspirants are temporary solutions that hide or even exacerbate the problem.

S. mutans is the major etiological agent of dental caries. Current methods (tooth brushing, antiseptic mouthrinses) to treat cariogenesis have focused on complete bacterial removal, i.e., elimination of S. mutans and other harmless oral bacteria. Caries have persisted despite these methods, and in many cases, S. mutans can become the dominant organism in the mouth. Several S. mutans and acid-targeted approaches (probiotic replacement, saliva pH adjustment) are under development, but none have shown clinical efficacy.

This example describes a number of STAMPs that preferentially or selectively reduce or eliminate S. mutans and/or Corynebacterium spp from mixed populations.

Several lead STAMPs with specific activity against Corynebacterium jeikeium are also disclosed herein.

The STAMPs described herein comprise functional regions within a peptide molecule or a chemical conjugate. These regions include a targeting region comprising one or more targeting moieties (e.g., targeting peptides), a linker, and one or more killing moieties (e.g., antimicrobial peptides (AMPs), porphyrins, etc.).

The STAMPs function through the targeting region, which selectively accumulates STAMPs, and therefore killing regions, on or in proximity to the microorganism of interest. Other flora are not recognized by the targeting region, and therefore avoid or have reduced STAMP accumulation and cellular damage.

In certain embodiments, STAMPs against oral S. mutans are best applied formulated in a mouthrinse, toothpaste, cream, gel, or adhesive strip, and in certain preferably embodiments, are provided in a formulation that comprises 0.5 to 2.5×PBS (or other salt) and other ingredients commonly found in oral healthcare formulations (e.g., mouthrinse formulations). Certain illustrative formulations are shown in Table 20.

During the course of evaluating STAMPs, antimicrobial peptides (AMPs), and binding peptides for desired activity, it was discovered that certain formulations can attenuate or promote peptide activity, as compared to activity levels in a default buffer system (1×PBS). In some cases, 1×PBS may provide the best level of activity. Below are a number of formulations that alter, or may alter, peptide or STAMP activity. For complex buffer systems, assume the base solvent is water unless otherwise stated.

Formulation 1 (1×PBS, pH 7.4): 136.8 mM NaCl, 2.68 mM KCl, 1.01 mM Na₂HPO₄, and 1.37 mM KH₂PO₄.

Formulation 2 (HEPES/CTAB): 20 mM HEPES (4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid), 150 mM NaCl, 1 mM MgCl₂, and 0.1% CTAB (Cetyl trimethylammonium bromide).

Formulation 3 (TRIS/CTAB): 20 mM Tris (tris(hydroxymethyl)aminomethane), pH 7.5, 150 mM NaCl, 1 mM MgCl₂, and 0.1% CTAB.

Formulation 4: 20 mM HEPES.

Formulation 5: 20 mM Tris, pH 7.5.

Formulation 6: 0.2% CTAB.

Formulation 7: 1% Glycerol.

Formulation 8: 1% Pluronic F108 (nonionic surfactant: α-Hydro-.omega.-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer).

Formulation 9: 1% Pluronic F123 (Poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol), average M_(n)˜5,800).

Formulation 10: 1% Pluronic F17R4 (Poly(propylene glycol)-block-poly(ethylene glycol)-block-polypropylene glycol), average M_(n)˜2,700).

Formulation 11: 1% to 7% PEG400.

Formulation 12: 50 mM Urea.

Formulation 13: 10 mM AOT (Sodium bis(2-ethylhexyl)sulfosuccinate).

Formulation 14: 0.5-0.1% Tween 20 (nonionic detergent, also known as polysorbate 20 or PEG(20)sorbitan monolauratesorbitan monolaurate).

Formulation 15: 0.5-0.1% Tween 80 (nonionic surfactant, C₆₄H₁₂₄O₂₆, also known as polyoxyethylene (20) sorbitan monooleate, (x)-sorbitan mono-9-octadecenoate poly(oxy-1,2-ethanediyl), or POE (20) sorbitan monooleate).

Formulation 16: 5-10% Ethanol.

Formulation 17: 20% Glycerin.

Formulation 18: 20% Sorbitol.

Formulation 19: 10% Glycerin/10% Sorbitol.

Formulation 20: 0.1% SLS (Sodium lauryl sulfate).

Formulation 21: 1% Pluronic F127 (nonionic surfactant: α-Hydro-.omega.-hydroxypoly(oxyethylene)poly(oxypropylene)poly(oxyethylene) block copolymer).

Formulation 21: 0.1% Tween 20 (nonionic detergent, also known as Polysorbate 20, or PEG(20)sorbitan monolaurate).

Formulation 21: 10% PG (phospholipid gel).

Mouthrinse neat solution #1 (made in 1×PBS): 7% ETOH, 20% Glycerin, 7% PEG 400, and 1% PLURONIC® F127.

Mouthrinse neat solution #2 (made in 1×PBS): 7% ETOH, 20% Sorbitol, 7% PEG 400, and 1% PLURONIC® F127.

Mouthrinse neat solution #3 (made in 1×PBS): 7% ETOH, 20% Glycerin and 7% PEG 400.

Mouthrinse neat solution #4 (made in 1×PBS): 7% ETOH, 20% Sorbitol and 7% PEG 400.

Other illustrative, but not limiting, mouthrinse formulations are shown in Table 20.

TABLE 20 Illustrative mouthrinse formulations. Rinse# ETOH Glycerin PEG400 F127 Water¹ Fluoride  1 5 22.5 7 1 64.5 187.5  2 6 25 1 0 68 0  3 6 20 7 0 67 0  4 6 20 1 1 72 0  5 7 25 7 0 61 0  6 7 20 1 0 72 0  7 7 20 7 0 66 250  8 5 20 7 1 67 0  9 6.472 21.139 5.361 0.722 66.306 250 10 7 22.5 1 0 69.5 250 11 5 25 1 0 69 250 12 7 20 7 0 66 250 13 5 20 1 1 73 250 14 5 25 7 0.5 62.5 250 15 7 25 1 0.5 66.5 250 16 7 25 7 1 60 250 17 5 25 7 0.5 62.5 0 18 7 20 1 1 71 250 19 6 25 1 1 67 250 20 7 25 7 1 60 125 21 5 25 1 0 69 250 22 5 20 1.5 0.5 73 0 23 7 20 1 1 71 250 24 6 20 1 0 73 250 25 5 22.333 3.778 0.444 68.444 125 26 7 25 1 1 66 0 27 6 25 7 0 62 250 28 7 20 7 1 65 0 29 7 25 4 1 63 62.5 30 5 25 4 0 66 0 31 5 25 1 1 68 0 32 7 25 7 1 60 0 33 7 22.5 4 0.5 66 0 34 5 20 4.5 0 70.5 250 35 5 23 1 0 71 62.5 36 6 20 1 1 72 0 37 5 20 7 1 67 250 38 7 20 1 0 72 0 39 5 25 4 1 65 250 40 5 22.5 7 0 65.5 0 n1 7 20 7 1 65 0 n2 7 20% 7 1 65 0 Sorbitol n3 7 20 7 0 66 0 n4 7 20% 7 0 66 0 Sorbitol ¹1xPBS can be substituted for water

In certain embodiments, Corynebacterium-specific STAMPs are formulated in any number of creams, nanoemulsions, lipid micelles, aqueous or no-aqueous gels, sprays, soaps or roll-on bars, or other products used for axilla or other hygiene.

STAMP-mediated selective antimicrobial activity can result in preservation of the normal flora at the oral or axilla mucosal surface, resulting in protective colonization and the conversion of a harmful flora to a beneficial one. Recurrence of pathogen overgrowth would be reduced, which also limits the amount and frequency (and therefore cost) of STAMP delivery. STAMPs allow for “surgical” antimicrobial precision, which limits antimicrobial resistance evolution as well due to the general mechanism of cell membrane damage mediated by the killing region.

A number of anti-S. mutans STAMPs (see Table 21) and anti-C. jeikeium STAMPs have been designed and tested, some in formulations. All show potent selective activity against their bacterial targets in vitro, including against biofilm forms. When tested, STAMPs have little cytotoxicity against cell lines in vitro.

TABLE 21 Illustrative anti-S. mutans STAMPs. Single underline is binding peptide. Double underline is antimicrobial peptide (AMP). No underline is linker. * indicates optionally protected (e.g., amidated) C terminal. SEQ STAMP Amino Acid Sequence ID NO 2_1G2 FIKHFIHRFGGGKNLRIIRKGIHIIKKY* 3230 C16AF5 TFFRLFNRSFTQALGKGGGFLKFLKKFFKKLKY* 3231 1845L621 KFINGVLSQFVLERKPYPKLFKFLRKHLL* 3232 1903-21 NIFEYFLEGGGKLFKFLRKHLL* 3233

TABLE 22 Illustrative anti-C. jeikeium STAMPs. Single underline is binding peptide. Double underline is antimicrobial peptide (AMP). No underline is linker. * indicates optionally protected (e.g., amidated) C terminal. SEQ STAMP Amino Acid Sequence ID NO 2038L6CAM GKAKPYQVRQVLRAVDKLETRRKKGGRPYPGWR 3234 135 LIKKILRVFKGL* 1619- SKRGRKRKDRRKKKANHGKRPNSGGGGWRLIK 3235 CAM135 KILRVFKGL* 1599- YSKTLHFADGGGKILKFLFKKVF* 3236 BD2.16 1619- SKRGRKRKDRRKKKANHGKRPNSGGGKILKFL 3237 BD2.16 FKKVF* 1904- GSVIKKRRKRMSKKKHRKMLRRTRVQRRKLGKG 3238 BD2.16 GGKILKFLFKKVF*

It was a surprising discovery that certain anti-S. mutans STAMPs required a salt in the formulation (e.g., PBS) for optimum activity. Thus, for example, the anti-S. mutans STAMP C16G2 (TFFRLFNRSFTQALGKGGGKNLRIIRKGIHIIKKY*, SEQ ID NO:2) comprising the TFFRLFNRSFTQALGK (SEQ ID NO:1) attached to the antimicrobial peptide (AMP) KNLRIIRKGIHIIKKY (SEQ ID NO: 3080) by a peptide linker (GGG) was substantially inactive in water-based salt-free buffers and nanoemulsions, but was active in a phosphate buffered saline (PBS) formulation. Suitable PBS formulations ranged from 0.5×PBS to about 2.5×PBS with an activity optimum at about 1×PBS. Similar results are believed to obtain for other anti-S. mutans STAMPS as well as a number of other STAMPs. In certain embodiments STAMP stability in solution was improved by inclusion of fluoride in mouthrinse.

Example 5 Photodynamic Therapy Targeted Against Streptococcus mutans

Dental caries (tooth decay) is one of the most prevalent and costly infectious diseases in the United States. Currently, the annual expenditures on dental services exceed $85 billion, with the majority of these costs attributable to dental caries and its sequelae (www.ada.org/). The oral cavity harbors a complex microbial community consisting of over 600 different non-harmful/commensal microbial species together with a limited number of pathogenic bacteria, including the major etiological agent of dental caries, Streptococcus mutans. Once established, S. mutans generates acid during the fermentation of dietary sugars, which causes the demineralization of tooth structure and inhibits the growth of non-pathogenic commensal bacteria within the same microbial niche. Despite diligent use of broad-spectrum antimicrobial compounds and tooth brushing, S. mutans persists within the oral cavity and causes repeated cycles of cariogenesis. Current “remove all, kill-all” approaches have shown limited efficacy, since a “cleaned” tooth surface provides an equal opportunity for commensal as well as pathogenic bacteria to re-colonize in the non-sterile environment of the oral cavity. To address this shortcoming, we have constructed and evaluated a light-activated S. mutans-selective antimicrobial agent. C16-RB, constructed via conjugation of the S. mutans competence-stimulating peptide to the photodynamic dye rose bengal, displays robust anti-S. mutans activity in vitro under blue exposure from a handheld dental curing light. C16-RB has reduced activity against other oral streptococci under mixed biofilm conditions and has limited cytotoxicity in vitro.

To develop a method of selectively eliminating S. mutans from a dental biofilm so that beneficial species exert a protective colonization effect and long-term protection from S. mutans re-colonization can be attained we created a novel class of targeted antimicrobials, known as specifically-targeted antimicrobial peptides, or STAMPs. STAMPs consist of functionally independent, yet conjoined, domains within a linear peptide sequence; a targeting region and an antimicrobial region. The targeting region, which binds specifically to a bacterial species of interest, delivers the killing portion of the molecule that consists of a normally wide-spectrum antimicrobial peptide. Previously, we successfully designed STAMPs against S. mutans by taking advantage of the competence stimulating pheromone (CSP) peptide produced by this organism that has demonstrated S. mutans-specific recognition. STAMPs synthesized with portions of CSP as targeting domains were capable of specific antimicrobial activity against S. mutans, and not other oral streptococci or non-cariogenic organisms in biofilms.

We hypothesized that targeted killing might be achieved through the use of non-peptide antimicrobial molecules, such as porphyrins or dyes utilized in PDT. Here we present the proof-of-principle construction and in vitro efficacy of the targeted, peptide-guided, photodynamic molecule C16-RB. C16-RB displays S. mutans selective antimicrobial activity upon blue light activation with limited activity against non-cariogenic oral streptococci and epithelial cells.

Materials and Methods

Synthesis of C16-RB

All amino acids, synthesis resins and reagents were peptide synthesis grade (Anaspec, San Jose, Calif.; Fisher Scientific). To construct our C16-RB conjugate, conventional 9-fluorenylmethoxy carbonyl (Fmoc) solid-phase methodology was employed to synthesize the CSP_(C16) peptide and attach the succinate and PEG linkers, utilizing double coupling cycles in N-hydroxybenzotrazole, HBTU (O-benzotriazole-N,N,N,N-tetramethyl-uronium hexafluoro-phosphate) and diisopropyl ethylamine (DIEA), with dimethylformamide (DMF) and N-methylpyrrolidone (NMP) as solvents, as described previously. The peptide resin (1 molar equivalent, 15 mg) was then swollen in DMF for 30 min prior to attachment of the PEG terminal amide group to the carboxyl lactone in RB (FIG. 19B). This reaction was carried out in a mixture of 2-(7-Aza-1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU, 5-molar excess) in dichloromethane (DCM):DMF:dimethylsulphoxide (DMSO) (1:1:1 (v/v)). Ten molar equivalents of DIEA were added to the reaction flask to initiate the reaction, which was protected with argon and stirred at room temperature for 5 h. After completion, the reaction mixture was passed down sintered glass filtered vial and extensively washed with DMF and DCM to remove all waste reagents. The resin was then dried overnight in vacuum, and cleaved with 1 mL of trifluoroacetic acid (TFA)/thioanisole/water/EDT (10/0.5/0.5/025) for 2 hr at room temperature. The cleavage solution was precipitated with 10 mL methyl-tert butyl ether, and the precipitate was washed twice with the same amount of ether. The crude product was purified via preparative-level HPLC (Source 15RPC column, ACTA purifier, Amersham) and eluted with gradient acetonitrile/water from 10 to 35% in 10 min, which was increased to 90% over 8 min before finally being washed 15 min with 95% acetonitrile.

C16-RB was purified further to >90% and the molecular mass confirmed via LC/MS, utilizing increasing hydrophobicity gradient of acetonitrile in water with 0.01% TFA as described above (Waters X-bridge BEH 130 C18 column, 4.6×100 mm, particle size 5 μm, Waters 3100 system). LC spectra were analyzed with MassLynx Softward v. 4.1 (Waters). C16-RB mass (3118.0) was confirmed by electrospray ionization (ESI) mass spectroscopy in linear, positive ion mode. The final product was lyophilized and protected from light at all times. C16-RB was soluble in 50% methanol.

Bacterial and Cellular Growth

Streptococcus oralis ATCC 10557, Streptococcus gordonii (Challis), Streptococcus sanguinis (NY101), Streptococcus mitis ATCC 903, Streptococcus salivarius ATCC 13419 and S. mutans wild-type UA140 and JM11 (spectinomycin-resistant) strains were grown in Todd-Hewitt (TH) broth 37° C. in an anaerobic atmosphere of 80% N₂, 10% CO₂, and 10% H₂. BHK-21 (ATCC CRL-10) fibroblasts were propagated in DMEM with 10% FBS, 1 mM sodium pyruvate, 100 units/mL penicillin G, and 100 μg/mL streptomycin at 37° C. with 5% CO₂. Cells were detached with 0.25% trypsin and subcultured as recommended by the supplier.

Photodynamic Antimicrobial Assays Against Biofilms

To evaluate C16-RB against monoculture biofilms, S. mutans UA140 was grown overnight in TH prior to inoculation for biofilm formation. For biofilms, 1:5000 dilution of overnight culture was made into TH with 1% sucrose in 2 mL centrifuge tubes (200 μL volume) and grown 24 h under anaerobic conditions. After incubation, biofilms were treated for 5 min with 5 or 25 μM C16-RB or 5 μM RB in 1×PBS, or PBS alone, followed by removal of supernatant and exposure to 5 min blue light (emission 400-550 nm, power 400 mW/cm²) from an Astralis 7 (Ivoclar Vivodent, Austria) handheld LED commonly used as a dental curing light. The light source was suspended 4 cm from the tube bottom (even with the mouth of the tube). A duplicate set of samples were left covered to serve as dark controls. After treatment, biofilms were mechanically disrupted and plated to determine cfu/mL.

To gauge C16-RB selectivity for S. mutans, similar assays were conducted against multispecies biofilms. Mixed biofilms were seeded by diluting (1:5000) a mixture of equal parts S. oralis, S. gordonii, S. mitis, S. sanguinis, S. salivarius, and S. mutans JM11 (made from overnight cultures) into TH with 1% sucrose, 1% glucose, and 1% mannose. Biofilms were incubated and treated as described above with the addition of vitamin C or potassium gluconate. After the addition of agent and 5 min incubation, biofilms were washed 1× with 1×PBS prior to light exposure. After PDT and biofilm disruption, survivors were plated on TH, and TH supplemented with 800 μg/mL spectinomycin, which allowed for quantitation of surviving total oral streptococci and surviving S. mutans, respectively.

Evaluation of C16-RB Cytotoxicity

The effect of RB and C16-RB on human fibroblasts was ascertained by utilizing the Promega CellTiterGlo assay, as described by the manufacturer. Briefly, fibroblasts were grown to confluence, detached, and seeded to ˜5,000 cells per well in a 96-well opaque walled, clear bottom 96-well plate (Nunc International). For long-term dark toxicity, cells were allowed to attach to for 18 h before the culture medium was replaced with medium plus serially-diluted RB or C16-RB (200 μM to 390 nM) or medium alone. After 18-24 h, equal volume Cell Titer Glo reagent was added to each well and mixed. Luciferace activity was then quantified to measure cell viability (Varian Fluorometer in Biolumenescence mode). To measure cytotoxicity after RB or C16-RB light exposure, cells were seeded at ˜10,000 cells per well and allowed to attach for 4 h. Cell growth medium was then replaced with RB or C16-RB containing medium, prior to exposure (a single well at a time) with blue light (400 mW/cm²) suspended ˜3 cm from the well bottom. After exposure, cultures were disrupted with Cell Titer Glo and luciferase activity quantitated as above.

Results

Design of Photodynamic Peptide-Dye Conjugate

For the targeting peptide component of the chimeric molecule, we selected a shortened derivative of S. mutans CSP, CSP_(C16) (sequence: TFFRLFNRSFTQALGK). CSP_(C16) has been utilized successfully as a STAMP targeting peptide in several constructs, and demonstrates selective binding to S. mutans and not other non-cariogenic bacteria. For the photodynamic dye, we selected rose bengal (RB, FIG. 19A), a xanthene dye with a demonstrated record of safety as a diagnostic tool in optometry. Unlike TBO or methylene blue, RB is not recognized by efflux pumps, and has shown robust activity against a variety of bacteria in vitro in the presence of green or blue light (max absorption ˜549 nm), and can be activated by a handheld dental curing LED.

C16-RB Synthesis

As shown in FIG. 19B, RB was attached to the N-terminus of CSP_(C16) through a succinate/PEG linker to construct the C16-RB molecule. Conventional solid-phase peptide methods were utilized to synthesize CSPC₁₆, followed by linker and RB coupling prior to cleavage from the resin. After cleavage, C16-RB was repeatedly purified by LC/MS prior to evaluation. As shown in FIG. 20, over 95% purity was achieved with the expected mass species observed. The lactone ring in RB was opened as a result of CSP_(C16) attachment. However, we hypothesized that the conjugate would retain enough singlet-oxygen generating activity for a proof-of-principle demonstration, as other xanthene dyes with activity lack this ring.

C16-RB Efficacy Against Single-Species S. mutans Biofilms

After synthesis, the basic photosensitization potential of C16-RB was assessed by challenging mature single-species S. mutans biofilms (grown 24 h) with C16-RB or unmodified RB, followed by blue emission from a dental curing light. As shown in FIG. 21, potent antimicrobial activity was observed in cultures exposed to C16-RB or RB and blue light: a reduction in over 3 log₁₀ from input cfu/mL at 5 or 25 μM. In contrast, appreciable decreases in cfu/mL were not observed in S. mutans treated with blue light alone, or 5 μM RB or C16-RB dark controls. Modest dark toxicity was observed in samples treated with 25 μM C16-RB. Overall, these results indicate that the peptide-dye conjugate is active against S. mutans and at roughly similar levels to the parental RB molecule.

Selective PDT Against Multi-Species Biofilms

C16-RB was next evaluated for selectivity in mixed cultures containing S. mutans and non-cariogenic oral streptococci that compete for the same niche on the tooth surface. We utilized mixed biofilms of S. mutans transformed with spectinomycin resistance (strain JM11, Merritt, et al., 2005), plus S. oxalis, S. gordonii, S. mitis, S. sanguinis, and S. salivarius. The mixed cultures were grown 24 and then treated with RB or C16-RB as indicated, plus potassium gluconate to minimize killing of untargeted bacteria by reducing the superoxide-producing activity of the free C16-RB not bound to S. mutans. Ethanol treatment served as an indiscriminant killing control. As shown in FIG. 21, RB alone exhibited strong indiscriminant photodynamic antimicrobial effects against S. mutans and non-S. mutans in the mixed biofilm system (ratio of surviving S. mutans:non-cariogenic streptococci cfu˜1). In contrast, C16-RB displayed specific photodynamic activity towards S. mutans, and not the other oral streptococci examined, as reflected in the low ratio of recovered S. mutans to other streptococci. These results suggest C16-RB has antimicrobial activity in the presence of blue light that is specific for S. mutans and dependent on the CSP_(C16) targeting peptide.

Cytotoxicity Against Eukaryotic Cells

Given the demonstrated PDT potential of RB-C16, experiments were conducted to examine the cytotoxicity for this conjugate and RB alone. IC₅₀s were obtained for BHK cells exposed C16-RB, RB, or Melittin B (positive control for cytotoxicity), with and without blue light exposure. As shown in Table 23, cytotoxicity was noted for cells exposed to Melittin B at the lowest peptide dilution tested at either 5 min or 24 h, with or without light (IC₅₀<1.56 μM), while light-dependent toxicity was observed only for RB-treated samples. No photo-associated toxicity was noted in BHK cells treated with C16-RB, though modest light-independent cytotoxicity (IC₅₀=90 μM) was detected after 24 h of exposure. These results suggest that C16-RB is not toxic to BHK cells after illumination, and displays mild toxic effects (when compared to Melittin B) after 24 h exposure.

TABLE 23 Cytotoxicity of RB and C16-RB compounds. IC₅₀ (μM) 5 min dark: BHK RB-C16 >100 RB >100 Melittin B  <1.56 5 min w/blue light: RB-C16 >100 RB 40 Melittin B  <1.56 24 h dark RB-C16 55 RB 90 Melittin B  <1.56

It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to persons skilled in the art and are to be included within the spirit and purview of this application and scope of the appended claims. All publications, patents, and patent applications cited herein are hereby incorporated by reference in their entirety for all purposes. 

What is claimed is:
 1. A chimeric construct, said construct comprising: a targeting peptide comprising the amino acid sequence LATKLKYEKEHKKM (SEQ ID NO:554), where said targeting peptide is attached to an antimicrobial peptide, wherein said targeting peptide is attached to said antimicrobial peptide directly or through a peptide linker and where said chimeric construct is a fusion protein.
 2. The chimeric construct of claim 1, wherein said antimicrobial peptide comprises an amino acid sequence found in Table 4, and/or Table 5, and/or Table 14, and/or Table
 15. 3. The chimeric construct of claim 1, wherein said targeting peptide is linked directly to said antimicrobial peptide.
 4. The chimeric construct of claim 1, wherein said targeting peptide is linked to said antimicrobial peptide via a peptide linker.
 5. The chimeric construct of claim 4, wherein said targeting peptide is attached to said antimicrobial peptide by a peptide linker comprising an amino acid sequence selected from the group consisting of AAA, GGG, GGGG (SEQ ID NO:3212), SGG, GGSGGS (SEQ ID NO:3213), SAT, PYP, PSPSP (SEQ ID NO:3216), ASA, ASASA (SEQ ID NO:3215), KKKK (SEQ ID NO:3217), RRRR (SEQ ID NO:3218), GGGGS (SEQ ID NO:3219), GGGGS GGGGS (SEQ ID NO:3220), GGGGS GGGGS GGGGS (SEQ ID NO:3221), GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3222), GGGGS GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3223), and GGGGS GGGGS GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3224).
 6. A pharmaceutical composition comprising a chimeric construct of claim 1 in a pharmaceutically acceptable carrier.
 7. A composition comprising a targeting peptide comprising the amino acid sequence LATKLKYEKEHKKM (SEQ ID NO:554), where said targeting peptide is attached to a photosensitizing agent, wherein said photosensitizing agent is selected from the group consisting of a porphyrin, a cyanine, and a phthalocyanine.
 8. The chimeric construct of claim 1, wherein said antimicrobial peptide comprises an antimicrobial peptide selected from the group consisting of FLKFLKKFFKKLKY (SEQ ID NO:1044), KLFKFLRKHLL (SEQ ID NO:1034), and KNLRIIRKGIHIIKKY (SEQ ID NO:3082).
 9. The chimeric construct of claim 1, wherein said construct bears one or more protecting groups.
 10. The chimeric construct according to claim 9, wherein said one or more protecting groups are independently selected from the group consisting of acetyl, amide, 3 to 20 carbon alkyl groups, Fmoc, Tboc, 9-fluoreneacetyl group, 1-fluorenecarboxylic group, 9-florenecarboxylic group, 9-fluorenone-1-carboxylic group, benzyloxycarbonyl, Xanthyl (Xan), Trityl (Trt), 4-methyltrityl (Mtt), 4-methoxytrityl (Mmt), 4-methoxy-2,3,6-trimethyl-benzenesulphonyl (Mtr), Mesitylene-2-sulphonyl (Mts), 4,4-dimethoxybenzhydryl (Mbh), Tosyl (Tos), 2,2,5,7,8-pentamethyl chroman-6-sulphonyl (Pmc), 4-methylbenzyl (MeBzl), 4-methoxybenzyl (MeOBzl), Benzyloxy (BzlO), Benzyl (Bzl), Benzoyl (Bz), 3-nitro-2-pyridinesulphenyl (Npys), 1-(4,4-dimentyl-2,6-diaxocyclohexylidene)ethyl (Dde), 2,6-dichlorobenzyl (2,6-DiCl-Bzl), 2-chlorobenzyloxycarbonyl (2-Cl—Z), 2-bromobenzyloxycarbonyl (2-Br—Z), Benzyloxymethyl (Bom), t-butoxycarbonyl (Boc), cyclohexyloxy (cHxO), t-butoxymethyl (Bum), t-butoxy (tBuO), t-Butyl (tBu), and Trifluoroacetyl (TFA).
 11. The chimeric construct of claim 9, wherein said construct comprises a protecting group at a carboxyl and/or amino terminus.
 12. The chimeric construct of claim 11, wherein a carboxyl terminus is amidated.
 13. The chimeric construct of claim 4, wherein said targeting peptide is attached to said antimicrobial peptide by a peptide linker consisting of an amino acid sequence selected the group consisting of AAA, GGG, GGGG (SEQ ID NO:3212), SGG, GGSGGS (SEQ ID NO:3213), SAT, PYP, PSPSP (SEQ ID NO:3216), ASA, ASASA (SEQ ID NO:3215), KKKK (SEQ ID NO:3217), RRRR (SEQ ID NO:3218), GGGGS (SEQ ID NO:3219), GGGGS GGGGS (SEQ ID NO:3220), GGGGS GGGGS GGGGS (SEQ ID NO:3221), GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3222), GGGGS GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3223), and GGGGS GGGGS GGGGS GGGGS GGGGS GGGGS (SEQ ID NO:3224).
 14. The chimeric construct of claim 1, wherein said targeting peptide ranges in length up to about 50 amino acids.
 15. The chimeric construct of claim 1, wherein the amino acid sequence of said targeting peptide consists of the sequence LATKLKYEKEHKKM (SEQ ID NO:554). 